Marek&#39;s disease herpesvirus DNA segment encoding glycoproteins, gD, gI and gE

ABSTRACT

DNA encoding glycoproteins gD, gI and gE from Marek&#39;s disease herpesvirus is described The DNA is useful for probes to detect the DNA in the herpesvirus, for expression to produce the glycoproteins that can be used for producing the antibodies which specifically recognize the three glycoprotein antigens, and in the case of the latter two genes for potential insertion sites for foreign genes and as possible sites for gene inactivation to attenuate MDV field isolates for vaccine purposes.

CROSS-REFERENCE TO RELATED APPLICATION

This application is a Division of Ser. No. 07/736,335, filed Jul. 25, 1991, which is a continuation-in-part of U.S. application Ser. No. 07/572,711, filed Aug. 24, 1990, now U.S. Pat. No. 5,138,033.

BACKGROUND OF THE INVENTION

(1) Field of the Invention

The present invention relates to segments of the Marek's Disease Herpesvirus genome, from its unique short (U_(S)) region encoding glycoproteins gD, gI and gE, and to novel glycoproteins produced therefrom In particular, the present invention relates to DNA segments containing genes encoding these glycoprotein antigens and containing potential promoter sequences up to 400 nucleotides 5' of each gene, segments which are useful for probing for Marek's disease herpesvirus, as a possible source for Marek's disease virus (MDV) promoters, for gene expression to produce the glycoproteins that in turn can be used for producing antibodies which recognize the three glycoprotein antigens, and in the case of the latter two genes, for potential insertion sites for foreign genes and as possible sites for gene inactivation to attenuate MDV field isolates for vaccine purposes

(2) Prior Art

MDV is an oncogenic herpesvirus of chickens, which is known to cause T cell lymphomas and peripheral nerve demyelination. The resulting disease, Marek's disease (MD), was the first naturally occurring lymphomatous disorder to be effectively controlled via vaccination, using either the antigenically related, yet apathogenic, herpesvirus of turkeys (HVT) or attenuated field isolates of MDV.

Because of similar biological properties, especially its lymphotropism, MDV has been classified as a member of the gammaherpesvirus subfamily (Roizman, B., et al., Intervirology 16:201-217 (1981)). Of the three herpesvirus subfamilies, gammaherpesviruses exhibit particularly marked differences with regard to genome composition and organization. For example, the B-lymphotropic Epstein-Barr virus (EBV) of humans has a 172.3 kbp genome with 60% G+C content, is bounded by terminal 0.5 kbp direct repeats and contains a characteristic set of internal 3.07 kbp tandem repeats (Baer, R., et al., Nature (London) 310:207-211 (1984)). Herpesvirus saimiri (HVS), a T-lymphotropic herpesvirus of new-world monkeys and lower vertebrates, has an A+T rich coding sequence (112 kbp; 36% G+C; i.e. L-DNA) without any large-scale internal redundancy, but contains instead greater than 30 reiterations of a 1.44 kbp sequence of 71% G+C at the termini of the genome (H-DNA) (Banker, A. T., et al., J. Virol. 55:133-139 (1985)). Despite the structural differences between EBV and HVS, the genomes of these two viruses encode serologically related proteins and share a common organization of coding sequences which differs from that of the neurotropic alphaherpesviruses, exemplified by herpes simplex virus (HSV) and varicella-zoster virus (VZV) (Camerion K. R., et al., J. Virol. 61:2063-2070 (1987); Davison, A. J., et al., J. Gen. Virol. 68:1067-1079 (1987); Davison, A. J., et al., J. Gen. Virol. 67:597-611 (1986); Davison, A. J., et al., J. Gen. Virol. 76:1759-1816 (1986); Davison, A. J., et al., J. Gen. Virol. 64:1927-1942 (1983); Gompels, U. A., J. of Virol. 62:757-767 (1988); and Nichols, J., et al., J. of Virol. 62:3250-3257 (1988)).

In contrast to other gammaherpesviruses, MDV has a genome structure closely resembling that of the alphaherpesviruses (Cebrian, J., et al., Proc. Natl. Acad. Sci. USA 79:555-558 (1982); and Fukuchi, K., et al., J. Virol. 51:102-109 (1984)). Members of the latter subfamily have similar genome structures consisting of covalently joined long (L) and short (S) segments. Each segment comprises a unique (U) segment (U_(L), U_(S)) flanked by a pair (terminal and internals) of inverted repeat regions (TR_(L), IR_(L) ; TR_(S) ; respectively) Alphaherpesviruses include human HSV and VZV, porcine pseudorabies virus (PRV), bovine herpesvirus (BHV) and equine herpesvirus (EHV). Because MDV contains extensive repeat sequences flanking its U_(L) region, its genome structure most resembles that of HSV (Cebrian, J., et al., Proc. Natl. Acad. Sci. USA 79:555-558 (1982); and Fukuchi, K., et al., J. Virol. 51:102-109 (1984)).

Recent studies (Buckmaster, A. E., et al., J. Gen. Virol. 69:2033-2042 (1988)) have shown that the two gammaherpesviruses, MDV and HVT, appear to bear greater similarity to the alphaherpesviruses, VZV and HSV, than to the gammaherpesvirus, EBV. This was based on a comparison of numerous randomly isolated MDV and HVT clones at the predicted amino acid level; not only did individual sequences exhibit greater relatedness to alphaherpesvirus genes than to gammaherpesvirus genes, but the two viral genomes were found to be generally collinear with VZV, at least with respect to the unique long (U_(L)) region. Such collinearity of U_(L) genes extends to other alphaherpesviruses such as HSV-1, HSV-2, EHV-1 and PRV as evidenced by both sequence analysis (McGeoch, D. J., et al., J. Gen. Virol. 69:1531-1574 (1988)) and DNA hybridization experiments (Davison, A. J., et al., J. Gen. Virol. 64:1927-1942 (1983)). Many of these U_(L) genes are shared by other herpesviruses, including the beta- and gammaherpesviruses (Davison, A. J., et al., J. Gen. Virol. 68:1067-1079 (1987)). The organization and comparison of such genes has suggested the past occurrence of large-scale rearrangements to account for the divergence of herpesviruses from a common ancestor. Unfortunately, such a hypothesis fails to account for the presence of alphaherpesvirus S component (unique shorts U_(S), and associated inverted/terminal repeat short, IR_(S), TR_(S)) genes which appear unique to members of this subfamily (Davison, A. J., et al., J. Gen. Virol. 68:1067-1079 (1987); Davison, A. J., et al., J. Gen. Virol. 67:597-611 (1986); and McGeoch, D. J., et al., J. Mol. Biol. 181:1-13 (1985)).

The DNA sequence and organization of genes in a 5.5 kbp EcoRl fragment mapping in the US region of MDV strain RBIB was described by Ross, Binns and Pastorek (Ross, L. J. N., et al, Journal of General Virology 72:949-954 (1991)). The properties and evolutionary relationships of four of the predicted polypeptides was also described (Ross, L. J. N. and M. M. Binns, Journal of General Virology, 72:939-947 (1991)). In that fragment they found the homologs of HSV US2, US3, US6 (gD) and US7 (gI), as well as an MDV specific gene. For the latter, only part of the gene was present. These reports confirm the presence of four MDV U_(S) genes, and the evolutionary relationship proposed above. It is important to note that no evidence for US8 (gE), or the genes to the left of US2 were described.

In addition to its uniqueness compared with beta- and gammaherpesviruses, the alphaherpesvirus U_(S) region is particularly interesting because of marked differences in its content and genetic organization within the latter subfamily (e.g. HSV-1 U_(S) =13.0 kbp, 12 genes, McGeoch, D. J., et al., J. Mol. Biol. 181:1-13 (1985)); VZV U_(S) =5.2 kbp, 4 genes, Davison, A. J., et al., J. Gen. Virol. 76:1759-1816 (1986)). In the case of HSV-1, 11 of the 12 U_(S) genes have been found to be dispensable for replication in cell culture (Longnecker, R., et al. , Proc. Natl. Acad. Sci. USA 84:4303-4307 (1987)). This has suggested the potential involvement of these genes in pathogenesis and/or latency (Longnecker, R., et al., Proc. Natl. Acad. Sci. USA 84:4303-4307 (1987); Meignier, B., et al., Virology 162:251-254 (1988); and Weber, P. C., et al., Science 236-576-579 (1987)). In the report by Buckmaster et al. (Buckmaster, A. E., et al., J. Gen. Virol. 69:2033-2042 (1988)), except for the identification of partial MDV sequences homologous to HSV immediate early protein alpha 22 (US1) and the serine-threonine protein kinase (US3), the contents localization and organization of MDV S component homologs was not determined Moreover, despite the presence of at least four HSV U_(S) glycoprotein genes (two in Vzv), no such homologs were identified.

In application Ser. No. 07/229,011 filed Aug. 5, 1988, (now abandoned), including Leland F. Velicer, one of the present inventors, the Marek's Disease herpesvirus DNA segment possibly containing the gene encoding the glycoprotein B antigen complex (gp100, gp60 gp49) was identified but not sequenced. Antigen B is an important glycoprotein complex because it can elicit at least partial protective immunity, and thus MDV DNA segment can be used for probes, as a possible source for promoters in the gene's 5' regulatory region, and for gene expression to produce the glycoproteins, which in turn can be used to produce antibodies that recognize the glycoprotein antigens. However, there was no discussion of the glycoproteins of the present invention. These B antigen glycoproteins are not encoded by the U_(S) region and thus are from a different region of the MDV genome.

In application Ser. No. 07/526,790, filed May 17, 1987, now abandoned, by Leland F. Velicer, the MDV herpesvirus DNA segment containing the gene encoding the glycoprotein A antigen (gp57-65) is described but not sequenced. This MDV DNA segment is useful as probes, as a possible source for promoters in the gene's 5' regulatory region, and for producing antibodies by the sequence of events described above. This DNA is also important because antigen A is now known to be a homolog of HSV gC, a gene non-essential for replication in cell culture. Since that property most likely also applies to the MDV homolog, it may be useful as a site for insertion of foreign genes. However, there was no discussion of the glycoproteins of the present invention. This glycoprotein is also not encoded by the Us region and is thus from a different region of the MDV genome.

Other glycoproteins are encoded by Marek's disease herpesvirus genome. In application Ser. No. 07/572,711, filed Aug. 24, 1990, now U.S. Pat. No. 5,138,033, by Leland F. Velicer, et al., the MDV DNA containing the genes encoding the MDV, gD, gI and part of gE glycoproteins is described, with MDV nucleotide sequences for the complete gD and gI genes and part of gE (MDV homologs of HSV genes US6, US7,US8, respectively). This MDV DNA segment is useful as probes, as a possible source for promoters in the gene's 5' regulatory region, and for producing antibodies by the sequence of events described above. The present invention is particularly directed to the complete gene (US8) encoding glycoprotein gE.

OBJECTS

It is an object of the present invention to provide sequenced DNA encoding glycoproteins gD, gI and gE, both together and individually. It is further an object of the present invention to provide DNA segments encoding these glycoprotein antigens and containing potential promoter sequences up to 400 nucleotides 5' of each gene; which are useful as DNA probes, as a possible source for MDV promoters, for producing antibodies which recognize the antigens and, in the case of the latter two glycoproteins, as insertion sites for foreign genes and as possible sites for gene inactivation to attenuate MDV field isolates for vaccine purposes. These and other objects will become increasingly apparent by reference to the following description and the drawings.

IN THE DRAWINGS

FIGS. 1A to C show map location, sequencing strategy and organization of MDV open reading frames (ORFs):

FIG. 1A includes MDV genomic structure and restriction maps outlining area sequenced.

FIG. 1B includes map location and sequencing strategy. Boxes define plasmid clones with BamHI, EcoRI or SalI-bound inserts that were used to generate M13mp18 and -19 templates for DNA sequencing. Rightward and leftward arrows define sequences derived from the top and bottom strands, respectively. The restriction enzyme sites are identified as: B=BamHI, E=EcoRI, Nc=NcoI, Ns=NsiI, S=SalI, and P=PstI. Sequences derived from random libraries (Sau3A, TaqI, RsaI), specific cloned restriction fragments, Bal 31-digested libraries or using synthetically-derived oligonucleotides are denoted by a, b, c, and d, respectively.

FIG. 1C includes organization of the MDV U_(S) ORFs. Numbers refer to homologs based on relation to HSV-1 U_(S) ORF nomenclature (McGeoch, D. J., et al., J. Mol. Biol. 181:1-13 (1985)). Boxes represent location of MDV ORFs. Arrows define direction of transcription/translation Names of ORFs are displayed above boxes. Potential polyadenylation signals on the top and bottom strands are highlighted by AATAAA and AAATAA, respectively. SORF1 and SORF2 are MDV-specific S component ORFs given arbitrary names.

FIG. 2 shows nucleotide and predicted amino acid sequences. The nucleotide sequence is given as the rightward 5' to 3' strand only (numbered 1 to 10350) (SEQ ID NO:1). Rightward- and leftward- directed predicted amino acid sequences are shown above and below the corresponding nucleotide sequences in single-letter code, respectively. The name of each ORF is given to the left of the first line of the amino acid sequence. Amino acid sequences are numbered from the first M (three letter code) (ATG in the DNA) at the N-terminus to the last amino acid at the C-terminus, which precedes the termination codon (identified by an *). Potential TATA consensus sites located within 400 nucleotides of the ATG are underlined and defined as sites containing at least six of seven matches to the TATA(AT)A(AT) consensus sequences defined by Corden et al. (Corden, B., et al., Science 209:1406-1414 (1980)). Underlines longer than seven nucleotides refer to areas containing overlapping TATA consensus sites.

FIG. 3A shows alignment of S component homologs (SEQ ID NOS:4-34) showing selected regions displaying maximum amino acid conservation. Gaps have been introduced to maximize alignment of identical amino acids as described in Methods. The consensus sequence (cons) indicates residues that are shared by at least all but one of the viruses and are indicated by capital letters. In alignments between more than two sequences, asterisks (*) indicate residues conserved by all of the viruses Amino acid numbers (with respect to 5'-ATG) of corresponding regions aligned are listed before and after each sequence.

FIG. 3B shows the dot matrix analyses depicting overall homologies between selected MDV-alphaherpesvirus S segment homolog comparisons. Points were generated where at least 15 amino acids over a sliding window length of 30 were found identical or similar. The resulting diagonals illustrate regions showing greatest conservation. Amino acid numbers (with respect to 5'-ATG) of corresponding sequences are denoted above and to the right of each plot.

FIG. 4 shows a comparison of overall genome organization of available S component ORFs (Audonnet, J.-C.,, et al., J. Gen. Virol. 71:2969-2978 (1990); McGeoch, D. J., et al., J. Gen. Virol. 68:19-38 (1987); Tikoo, S. K., et al., J. Virol. 64:5132-5142 (1990); Van Zijl, M., et al., J. Gen. Virol. 71:1747-1755 (1990); Zhang, G., et al., J. Gen. Virol. 71:2433-2441 (1990); Cullinane, A. A., et al., J. Gen. Virol. 69:1575-1590 (1988); Davison, A. J., et al., J. Gen. Virol. 76:1759-1816 (1986); McGeoch, D. J., et al., J. Mol. Biol. 181:1-13 (1985); Petrovskis, E. A., et al., Virology 159:193-195 (1987); Petrovskis, E. A., et al., J. Virol. 60:185-193 (1986); and Petrovskis, E. A., et al., J. Virol. 59:216-223 (1986)). Numbers above each ORF refer to homologs based on relation to HSV-1 U_(S) ORF nomenclature (McGeoch, D. J., et al., J. Mol. Biol. 181:1-13 (1985)). Alternative polypeptide designations common to each system are listed below those ORFs where applicable. Upper and lower case solid bars refer to rightward and leftward-directed ORFs, respectively Arrows refer to identified IR_(S) -U_(S) and/or U_(S) -TR_(S) junction sites.

FIG. 5 shows the sequence of steps necessary to produce a complete segment of Marek's disease herpesvirus DNA encoding glycoprotein gI and the part of gE included in the application filed Aug. 24, 1990.

GENERAL DESCRIPTION

The present invention relates to a segment of DNA of Marek's disease herpesvirus genome encoding multiple glycoproteins, and containing potential promoter sequences up to 400 nucleotides 5' of each gene, between a 1 and 10350 nucleotide sequence as shown in FIG. 2 (and identified as SEQ ID No:1).

Further, the present invention relates to an EcoRl I segment of Marek's disease herpesvirus genome encoding the glycoprotein D precursors and subsegments of the DNA.

Furthers stills the present invention relates to a segment of DNA encoding glycoprotein gD precursor between a 5964 and 7172 nucleotide sequence of Marek's disease herpesvirus DNA, and containing potential promoter sequences up to 400 nucleotides 5' of each genes as shown in FIG. 2 (and identified as part of SEQ ID No.:1) and subsegments of the segment of DNA which recognize the DNA.

The present invention also relates to a segment of DNA encoding glycoprotein gI precursor between a 7282 and 8346 nucleotide sequence of Marek's disease herpesvirus DNA, and containing potential promoter sequences up to 400 nucleotides 5' of each genes as shown in FIG. 2 (and identified as part of SEQ ID No:1) and subsegments of the segments that recognize the DNA.

The present invention also relates to a segment of DNA encoding glycoprotein gE precursor between a 8488 and 9978 nucleotide sequence of Marek's disease herpesvirus DNA, and containing potential promoter sequences up to 400 nucleotides 5' of each genes as shown in FIG. 2 (and identified as part of SEQ ID No:1) and subfragments of the DNA that recognize the DNA.

Furthers the present invention relates to the novel glycoprotein precursors which are produced by expressions of the genes in the segments of DNA.

Further the present invention relates to the potential MDV gene promoters, which are located in the 400 nucleotides 5' of each coding sequence.

SPECIFIC DESCRIPTION

The present invention shows a sequence analysis of a 10.35 kbp DNA stretch encompassing a majority of the MDV U_(S) region. Altogether seven MDV U_(S) homologs, including three glycoprotein genes and two additional MDV-specific open reading frames, were identified.

EXAMPLE 1 Materials and Methods

Recombinant Plasmids, M-13 subcloning and DNA sequencing

MDV EcoRl-0 and EcoRl-I of the pathogenic GA strain were previously cloned into pBR328 (Gibbs, C. P., et al., Proc. Natl. Acad. Sci. USA 81:3365-3369 (1984)), (Silva, R. F., et al.,, J. Virol. 54:690-696 (1985)) and made available by R. F. Silva, USDA Avian Disease and Oncology Lab, East Lansing, Mich., where these clones are maintained. GA strain BamHI-A and BamHI-Pl were previously cloned into pACYC184 and pBR322, respectively (Fukuchi, K., et al., J. Virol. 51:102-109 (1984)) and kindly provided by M. Nonoyama, Showa University Research Institute, St. Petersburg, Fla. GA strain clone GA-02, an EMBL-3 clone containing a partially digested MDV SalI insert, which contains BamHI-A, -Plo and additional 5' and 3' flanking sequences (kindly provided by P. Sondermeier, Intervet Intl. B. V., Boxmeer, The Netherlands) was used to extend analysis to the right of the above EcoRl and BamHl fragments. This phage clone was used to generate pUC18 subclones with smaller Sal I-bound inserts (psP18-A, pSP18-B, and pSP18-C) containing the 3' BamHI-Pl-flanking region. These clones (FIG. 1B) were used to generate M13mp18 and -19 subclones for use as templates for nucleotide sequencing. Small- and large-scale plasmid preparations were made using the alkaline lysis procedure (Maniatis, T., et al., Molecular cloning: a laboratory manual. Cold Spring Harbor Laboratory, Cold Spring Harbor, New York (1982)).

M13mp18 and M13mp19 phage subclones to be used as templates for sequencing were generated using specific restriction subfragments determined by restriction mapping or the use of Sau3A, Taq I or RsaI-digested viral DNA pools ligated into the unique BamHI, AccI or SmaI sites of M13 RF DNA, respectively. In some cases overlapping M13 deletion clones were obtained by processive Bal3l digestions from AccI, NaeI or NsiI restriction sites in EcoRl-0 by the method of Poncz et al (Poncz, M., et al., Proc. Natl. Acad. Sci. USA 79:4298-4302 (1982)) Standard methods (Maniatis, T., et al., Molecular cloning: a laboratory manual. Cold Spring Harbor Laboratory, Cold Spring Harbor, New York (1982)) were used for restriction digestions, gel electrophoresis, purification of DNA fragments from agarose gels, ligations and fill-in of 5' overhangs with Klenow fragment.

Ligated M13 products were transformed into CaCl₂ -competent JM107 host cells and added to melted B top agar containing 10 l of 100 mM IPTG, 50 l of 2% X-gal and 200 l of a fresh overnight JM101 culture. These contents were then plated onto B agar plates and incubated at 37° C. overnight, Recombinant (clear) plaques were then used to infect 5 ml of YT media diluted 1:50 with an overnight JM101 culture and rotated at 37° C. for 6 hours. The resulting cells were pelleted by centrifugation for 5 minutes at room temperature and the supernatants were removed and stored at 4° C. to retain viral stocks of each recombinant clone.

Using the recovered supernatants, single-stranded M13 phage DNA to be used as templates for DNA sequencing by the dideoxy-chain termination method was isolated according to instructions in the M13 Cloning/Dideoxy Sequencing Instruction Manual provided by Bethesda Research Laboratories, Recombinant M13mp phages were further screened by electrophoresing purified single-stranded viral DNA on 1% agarose mini-gels and selecting those templates showing reduced mobility in comparison to single-stranded M13mp 18 control DNA.

DNA sequencing with single-stranded M13 templates was performed by the dideoxy-chain termination method (Sanger, F. S., et al., Proc. Natl. Acad. Sci. USA 74:5463-5467 (1977)) employing the modified T7 DNA polymerase, "Sequenase" (United States Biochemical Corp., Cleveland, Ohio). A summary of the sequencing strategy is included in FIG. 1B. For DNA sequencing reactions, the specific step by step instructions provided with the Sequenase™ sequencing kit were employed. Briefly, single-stranded M13 templates were first annealed with the universal M13 synthetic oligonucleotide primer by incubation at 65° C. for 2 minutes followed by slow cooling until the incubation temperature was below 30° C. Following the addition of proper mixtures of deoxy- and dideoxynucleotide triphosphates (dNTPs and ddNTPs, respectively), radioactively labeled deoxyadenosine 5'-(alpha-thio) triphosphate (³⁵ S-dATP, 1000-1500 Ci/mmol; NEN-DuPont) and the "Sequenase" enzyme, synthesis of radioactively labeled complementary strands was initiated from the annealed primer. Four separate synthesis reactions were each terminated by the incorporation of the specific ddNTP (ddATP, ddGTP, ddTTP or ddCTP) used in each tube. Reaction products were electrophoresed through 7% polyacrylamide/50% urea/Tris-Borate-EDTA gels and the labeled chains were visualized by autoradiography. Both strands were sequenced at least once. This was facilitated by the use of 16 synthetic 17-mer olignonucleotides generated based on previously determined sequences and substituted for the universal primer under similar reaction conditions above (0.5 pmoles/reaction) according to the general approach described by Strauss (Strauss, E. C., et al., Anal. Biochem. 154:353-360 (1986)).

Analysis of sequence data

Sequences were assembled and analyzed on an IBM personal System 2/Model 50 microcomputer utilizing the IBI/Pustell (Pustell, J., et al., Nucl. Acids. Res. 14:479-488 (1986)) and Genepro (Version 4.10; Riverside Scientific Enterprises, Seattle, Wash.) sequence analysis software packages or programs obtained from the University of Wisconsin Genetics Computer Group (GCG; Devereaux, J., et al., Nucl. Acids. Res. 12:387-395 (1984)) and run on a VAX 8650 minicomputer. Database searches of the National Biochemical Research Foundation-Protein (NBRF-Protein, Release 21.0, 6/89) were made with the GCG program FASTA (Pearson, W. R., et al., Proc. Natl. Acad. Sci. USA 85:2444-2448 (1988)) which uses: (1) a modification of the algorithm of Wilbur and Lipman (Wilbur, W. J.. et al., Proc. Natl. Acad. Sci. USA 80:726-730 (1983)) to locate regions of similarity; (2) a PAM250-based scoring system (Dayhoff, M. O., et al., p. 345-352. In M. O. Dayhoff (ed.), Atlas of protein sequence and structure, vol. 5,, Suppl. 3. National Biomedical Research Foundation,, Washington, D.C. (1978)) and (3) the alignment procedure of Smith and Waterman (Smith, T. F., et al., Adv. Appl. Mathematics 2:482-489 (1981)) to join together, when possible,, the highest-scoring,, non-overlapping regions in order to derive an alignment and its resulting, optimized score. Dot matrix homology plots were generated by using the GCG program DOTPLOT with the output file from GCG's COMPARE. The latter creates a file of the points of similarity between two predicted amino acid sequences for which a window length of 30 and a stringency of 15 (in which conservative amino acid replacements are scored positive) were chosen. Using the GCG program GAP, specific amino acid sequences were aligned using the algorithm of Needleman and Wunsch (Needleman,, S. B., et al., J. Mol. Biol. 48:443-453 (1970)); following the insertion of gaps (to maximize the number of matches) the percentage of identical and similar amino acid residues were determined. To create multiple alignments using GAP, output files of gapped MDV sequences were created following successive GAP comparisons between the MDV sequence and its homologous sequences (in descending order of homology). These output files were used as input sequences for subsequent runs of GAP until the alignment of these gapped sequences could no longer be expanded by the addition of new gaps. Following alignments the gapped output files were displayed and a consensus sequence calculated using the GCG program PRETTY. To achieve optimal results, in some cases manual editing was employed (using GCG's LINEUP).

Results

The 10,350 nucleotide DNA sequence presented (FIG. 2) appears to encompass a majority of the MDV (GA) genome's unique short (U_(S)) region. A summary of the sequencing strategy is included in Materials and Methods and is depicted in FIG. 1B. This sequence spans the U_(S) fragments, EcoRl-0, EcoRl-I and extends to a SalI site 1.55 kbp downstream of the 3' end of BamHI-P₁ (FIGS. 1A and 1B). Fukuchi et al. (Fukuchi, K., et al., J. Virol. 51:102-109 (1984)) have previously mapped the IR_(S) -U_(S) junction to a 1.4 kb Bgl I fragment located in the second of five EcoRl subfragments of BamHI-A (FIG. 1B). Thus, the sequence presented here should lack between 2.6 and 4.0 kb of the 5'-proximal U_(S) region, assuming the above IR_(S) -U_(S) junction location can be independently confirmed. Because the region sequenced does not extend a sufficient distance downstream of BamHI-P₁, the MDV U_(S) -TR_(S) junction has not yet been precisely defined (Davison, A. J., et al., J. Gen. Virol. 76:1759-1816 (1986)). For VZV, EHV-4 and HSV-1, this border is located about 100 bp upstream, or 1.1 and 2.7 kb downstream, respectively, of the termination codon of their respective US8 homologs (Cullinane, A. A., et al., J. Gen. Virol. 69:1575-1590 (1988); Davison, A. J., et al., J. Gen. Virol, 76:1759-1816 (1986); and McGeoch, D. J., et al., J. Gen. Virol. 69:1531-1574 (1988)).

The overall G+C content of the region sequenced was found to be 41%, somewhat below the genomic MDV G+C values of 46% (Lee, L. F., et al., J. Virol. 7:289 (1971)). Observed frequencies of CpG dinucleotides in the whole sequence, or in the coding regions only, did not differ significantly from those expected from their mononucleotide compositions (data not shown). This result agrees with those obtained from alphaherpesviruses, while contrasting with those obtained from gammaherpesviruses, such as the A+T rich HVS and the G+C rich EBV, which are both deficient in CpG dinucleotides (Honess, R. W., et al., J. Gen. Virol. 70:837-855 (1989)).

The region sequenced contains 9 complete ORFs likely to code for proteins (FIG. 1C, basis for names is given below). This prediction was based on: (1) homology and positional organization comparisons to other alphaherpesvirus genes and (2) presence of potential TATA and polyadenylation consensus sequences (Birnstiel, M. L., et al., Cell 41:349-359 (1985); and Corden, B., et al., Science 209:1406-1414 (1980)), and (3) possession of favorable contexts for translational initiation (Kozak, M., J. Cell Biool. 108:229-241 (1989)). This identification was further guided by the observation that alphaherpesviruses such as HSV and VZV tend to contain relatively tightly packed, unspliced and generally nonoverlapping coding regions (Davison, A. J., et al., J. Gen. Virol. 76:1759-1816 (1986); Davison, A. J., et al., J. Gen. Virol. 76:1759-1816 (1986); McGeoch, D. J., et al., J. Gen. Virol. 69:1531-1574 (1988); McGeoch, D. J., et al., J. Mol. Biol. 181:1-13 (1985); and McGeoch, D. J., et al., J. Gen. Virol. 68:19-38 (1987)). Such genes, especially those of the U_(S) regions, often share polyadenylation signals, thereby resulting in 3'-coterminal mRNA families (Rixon, F. J., et al., Nucl. Acids Res. 13:953-973 (1985)). Methods for detecting protein coding regions based on the use of MDV-derived codon frequency tables (using these and previously published MDV sequences, Binns, M. M. , et al. , Virus Res. 12:371-382 (1989); Ross, L. J. N., et al., J. Gen. Virol. 70:1789-1804 (1989); and Scott, S. D., et al., J. Gen. Virol. 70:3055-3065 (1989)) or analysis of compositional bias (using the GCG programs CODONPREFERENCE and TESTCODE) were largely inconclusive, suggesting that MDV possesses relatively low codon and compositional biases compared to those prediced based on its mononucleotide composition. However, using the GCG program FRAMES, together with the MDV-derived codon frequency table above, the 9 identified ORFs clearly show a significantly low pattern of rare codon usage, which sharply contrasts with that observed in all other potentially translatable regions (data not shown).

The predicted amino acid sequences of the predicted ORFs (beginning from the first ATG codon) are shown relative to the nucleotide sequence in FIG. 2. Potential TATA sites within 400 nucleotides of the initiation codon are underlined. Proposed ORF and potential polyadenylation signal locations, identification of the -3, +4 ATG context nucleotides (Kozak, M., J. Cell Biol. 108:229-241 (1989)), as well as the lengths, relative molecular masses and predicted isoelectric points of the predicted translational products are shown in Table 1.

A summary of MDV data is shown in Table 1, with location of ORFs, predicted polyadenylation signals utilized, translational context nucleotides, lengths, relative molecular sizes and isoelectric points of predicted translation products.

                  TABLE 1                                                          ______________________________________                                                             Pre-   -3,+4       Pre-                                         dicted ATG.sup.a  dicted.sup.b                                                 Poly- Context  Molecu- Pre-                                                  ORF ORF adenyla- Nucleo- Length lar Size dicted                               Name Start End tion Site tides (aa) (kDa) pI.sup.c                           ______________________________________                                         US1   248    784    1777   A,A   179   20.4  6.5                                 US10 1077 1715 1777 G,G 213 23.6 8.2                                           SORF1 2884 1832 1790 A,A 351 40.6 8.2                                          US2 3923 3114 1790 A,G 270 29.7 7.6                                            US3 4062 5240 5394 A,G 393 43.8 6.1                                            SORF2 5353 5793 5904 C,G 147 16.7 9.8                                          US6 5964 7172 10040 G,G 403 42.6.sup.d 10.3.sup.d                              US7 7282 8346 10040 G,T 355 38.3.sup.d 6.7.sup.d                               US8 8488 9978 10040 A,T 497 53.7.sup.d 8.0.sup.d                             ______________________________________                                          .sup.a Nucleotides listed relative to -3, +4 positions, respectively;          numbering begins with the A of the ATG (AUG) codon as position +1;             nucleotides 5' to that site are assigned negative numbers.                     .sup.b In absence of posttranslational modifications.                          .sup.c Calculated using the GCG program, ISOELECTRIC.                          .sup.d Based on sequences that follow the predicted signal peptide             cleavage site.                                                           

In the absence of previous information concerning these MDV ORFS, and to simplify identifications they have been named (FIG. 1C, Table 1) based on homologous relationships to HSV-1 encoded U_(S) ORFs (McGeoch, D. J., et al., J. Mol. Biol. 181-1-13 (1985)). When appropriate, the letters MDV will preface the homolog's name to indicate the ORF's origin. The two MDV-specific ORFs have been arbitrarily named SORF1 and SORF2, based on their location in the S component.

According to the scanning model for translation, the 40S ribosomal subunit binds initially at the 5'-end of mRNA and then migrates, stopping at the first AUG (ATG) codon in a favorable context for initiating translation (Kozak, M., J. Cell Biol. 108:229-241 (1989)). However, in the absence of S1 nuclease and/or primer extension analysis, definitive start sites for translation cannot be accurately predicted. Nevertheless, likely start sites are listed in Table 1; these refer to the location of the first inframe ATG codon found in the major open reading frame. According to Kozak (Kozak, M., J. Cell Biol. 108:229-241 (1989)), as long as there is a purine in position -3, deviations from the rest of the consensus only marginally impair initiations In the absence of such a purine, however, a guanine at position +4 is essential for efficient translations Table 1 shows that all of the ORFs, except for SORF2, contain the important purine residue in the -3 position. Nevertheless, in the case of SORF2, a compensating guanine in position +4 is indeed present.

In the case of MDV US1, two transcriptional cap sites have been tentatively identified by 5' S1 nuclease protection analysis (data not shown). These sites appear to be located 18 and 25 nucleotides downstream of a TATATAA sequence at position 200 and 207, respectively (FIG. 2) Based on 3' S1 data, this transcript utilizes a polyadenylation signal located just downstream of the US10 coding region (Table 1 data not shown). Comparative Northern blot analyses of the U_(S) region indicate that the MDV US1 transcript appears to be the most prominent transcript expressed at late times (72 h) post-infection when extensive cytopathic effects are observed (data not shown). Phosphonoacetic acid inhibition studies have indicated that MDV US1 in contrast to its immediate-early HSV1 US1 counterparts is regulated as a late class gene (data not shown).

Using the computer program FASTA (Pearson, W. R., et al., Proc. Natl. Acad. Sci. USA 85:2444-2448 (1988)) with a K-tuple value of 1, each of the 9 predicted amino acid sequences was screened against the NBRF-Protein database (Release 21.0, 6/89), and recently published EHV-4 S segment gene sequences (11). Optimized FASTA scores of greater than 100 were generally considered to indicate a significant degree of amino acid similarity The results of this analysis are in Table 2.

                                      TABLE 2                                      __________________________________________________________________________     PAIRWISE COMPARISONS OF MDV AND ALPHAHERPESVIRUS S COMPONENT HOMOLOGS          __________________________________________________________________________                 US1                 US10                                                 Virus MDV HSV-1                                                                              VZV PRV                                                                               EHV-4                                                                               MDV                                                                               HSV-1                                                                              VZV EHV-4                               __________________________________________________________________________       % similar  MDV -- 47/26 43/27 51/33 48/30 -- 45/24 40/24 45/29                 % identical HSV-1 47/26 -- 49/29 43/25 50/29 45/24 -- 49/27 49/27                                                         VZV 43/27 49/29 -- 51/35                                                     54/36 40/24 49/27 -- 55/32                                                       PRV 51/33 43/25 51/35 --                                                     56/41 .sup.a .sup.a .sup.a                                                     .sup.a                                 EHV-4 48/30 50/29 54/36 56/41 -- 45/29 49/27 55/32 --                         FASTA MDV 891   101   160   218   208 1,071   134 147   251                    scores HSV-1 101 2,047   119   201   150   134 1,617 123   180                  VZV 160   119 1,378   340   359   147   123 978   191                          PRV 218   201   340 1,724   525 .sup.a .sup.a .sup.a .sup.a                    EHV-4 208   150   359   525 1,308   251   180 191 1,312                        Length (aa) 179   420   278   364  *273   213   312 180   259               __________________________________________________________________________                 US2               US3                                                    Virus MDV    HSV-1                                                                              PRV    MDV                                                                               HSV-1 VZV                                                                               PRV                                  __________________________________________________________________________       % similar  MDV -- 51/33 48/26 -- 56/38 54/33 55/33                             % identical HSV-1 51/33 -- 50/31 56/38 -- 57/41 59/36                           VZV .sup.a .sup.a .sup.a 54/33 57/41 -- 58/35                                  PRV 48/26 50/31 -- 55/33 59/36 58/35 --                                        EHV-4 .sup.a .sup.a .sup.a .sup.a .sup.a .sup.a .sup.a                        FASTA MDV 1,421     335 **118  1,931   611   616   563                         scores HSV-1 335 1,554 112   611 2,409   717   620                              VZV .sup.a .sup.a .sup.a   616   717 1,960   595                               PRV **168    112 1,240     563   620   595 1,948                               EHV-4 .sup.a .sup.a .sup.a .sup.a .sup.a .sup.a .sup.a                         Length (aa) 270   291 256   393   481   393   390                           __________________________________________________________________________                 US6               US7                                                    Virus MDV                                                                               HSV-1                                                                              PRV                                                                               EHV-1                                                                              BHV-1                                                                              MDV                                                                               HSV-1                                                                              VZV                                                                               PRV                                                                               EHV-1                               __________________________________________________________________________       % similar  MDV -- 42/21 44/23 43/21 42/33 -- 39/22 46/23 43/25 41/23                                                     % identical HSV-1 42/21 --                                                    47/27 44/22 50/28 39/22 --                                                     43/24 41/26 42/23                      VZV .sup.b .sup.b .sup.b .sup.b .sup.b 46/23 43/24 -- 47/25 46/29                                                        PRV 44/23 47/27 -- 51/30                                                     57/38 43/25 41/26 47/25 --                                                     51/30                                  EHV-1 43/21 44/22 51/30 -- 52/30 41/23 42/23 46/29 51/30 --                    BHV-1 42/33 50/28 57/38 52/30 -- .sup.a .sup.a .sup.a .sup.a .sup.a                                                     FASTA MDV 2,068   211   279                                                   246   291 1,816   145   228                                                    184   242                             scores HSV-1   211 1,999   294   253   304   145 1,880   234   188                                                      249                                    VZV .sup.b .sup.b .sup.b .sup.b .sup.b   228   234 1,705   198   298                                                     PRV   279   294 2,116   428                                                   730   188   188   198 1,652                                                   274                                    EHV-1   246   253   428 1,995   494   242   249   298   274 1,979                                                        BHV-1   291   304   730                                                      494 2,148 .sup.a .sup.a .sup.a                                                 .sup.a .sup.a                          Length (aa)   403   394   402   395   417   355   390   354   350           __________________________________________________________________________                                                424                                               US8                                                                      Virus MDV     HSV-1                                                                              VZV     PRV  EHV-1                                   __________________________________________________________________________       % similar  MDV -- 44/22 43/22 46/28 47/22                                      % identical HSV-1 44/22 -- 46/27 49/28 41/23                                    VZV 43/22 46/27 -- 47/25 46/29                                                 PRV 46/28 49/28 49/29 -- 54/34                                                 EHV-1 47/22 41/23 50/28 54/34 --                                               BHV-1 .sup.a .sup.a .sup.a .sup.a .sup.a                                      FASTA MDV 2,489     192   376 **243    399                                     scores HSV-1 192 2,751   357 257   274                                          VZV 376   357 3,171 329   468                                                  PRV **217    257   329 2,923     417                                           EHV-1 399   274   468 417 2,821                                                BHV-1 .sup.a .sup.a .sup.a .sup.a .sup.a                                       Length (aa) 497   550   623 577   552                                       __________________________________________________________________________      .sup.a existence of homolog undetermined                                       .sup.b no homolog present in genome                                            *actual length will differ somewhat, since probable initiation codon not       defined                                                                        **different score when order of comparison reversed                      

While SORF1 and SORF2 do not appear to share any significant homology to any of the sequences in the database (data not shown), apart from MDV US3, the other six ORFs (MDV US1, 10, 2, 6, 7, and 8; Tables 1, 2) were found to be homologous to alphaherpesvirus S segment genes exclusively (Table 2). Because the US3 ORF represents a member of the serine-threonine protein kinase superfamily (Hanks, S. K., et al., Science 241:42- (1988)), a relatively large number of scores above 150 were obtained. Nevertheless, these scores were 3-4 fold lower than those obtained in comparisons with US3 homologs of HSV, PRV and VZV. To compare with previously established alphaherpesvirus S segment homologies, all possible FASTA comparisons between the seven groups of alphaherpesvirus-related sequences are included. The program GAP was used in similar pairwise comparisons to generate optimal alignments in order to determine the total percentage of identical and similar amino acids shared by the two sequences As shown in Table 2, homology comparisons between MDV S segment ORFs and their alphaherpesvirus counterparts were comparable to those previously observed between the other alphaherpesvirus S segment homologs themselves. In some cases MDV ORFs were found to be more related to alphaherpesvirus homologs than those same homologs were to their other alphaherpesvirus counterparts (compare MDV/EHV-4 vs. HSV-1/EHV-4 US1 and MDV/EHV-4 vs. HSV-1/EHV-4 US10 homologies). Moreover, despite the fact that VZV lacks US2 and US6 homologs, MDV, although formally considered a gammaherpesvirus, clearly does possess US2 and US6 homologs. The results of limited multiple alignments for each of the seven homologs in which areas showing best conservation are depicted in FIG. 3A.

Dot matrix homology plots depicting overall homologies between selected MDV-alphaherpesvirus S segment homolog comparisons are included in FIG. 3B. (Using a sliding window length of 30 amino acids, in which points are generated where at least 15 amino acids are found identical or similar). The resulting diagonals illustrate the regions showing greatest conservation. Such regions include and in some cases extend upon those regions depicted in FIG. 3A.

More sensitive attempts to identify other related proteins not detected with FASTA were made using the GCG programs PROFILE and PROFILESEARCH. Use of these programs permit database comparisons which rely on information available from structural studies and, in this case, from information implicit in the alignments of related S component ORFs (including MDV sequences using GAP) (Gribskov, M., et al., Proc. Natl. Acad. Sci. USA 84:4355-4358 (1987)); nevertheless, such analyses failed to extend upon the groups of related proteins described here.

Herpesvirus glycoprotein homologs have generally been found to contain similar patterns of conserved cysteine residues. In comparing the gB homologs of seven different herpesviruses included in the alpha-, beta- and gammaherpesvirus subclasses, there is complete conservation of 10 cysteine residues (Ross, L. J. N., et al., J. Gen. Virol. 70:1789-1804 (1989)). HSV-1 US6 (gD) contains 7 cysteine residues: six appear critical for correct folding, antigenic structure and extent of oligosaccharide processing (Wilcox, W. C., et al., J. Virol. 62:1941-1947 (1988)). Not only is this same general pattern of cysteines conserved in the gD homologs of HSV-2 (McGeoch, D. J., et al., J. Gen. Virol. 68:19-38 (1987)) and PRV (Petrovskis, E. A., et al., J. Virol. 59:216-223 (1986)), but they are conserved in the MDV gD homolog as well (full alignment not shown). FIG. 3A depicts portions of cysteine conservation patterns observed among the US6 (gD), US7 (gI), and US8 (gE) homologs (in which case 4, 3, and 6 conserved cysteine residues are shown, respectively) While the MDV, VZV, PREV, and EHV-1 US8 homologs (Audonnet, J.-C., et al., J. Gen. Virol. 71:2969-2978 (1990); Davison, A. J., et al., J. Gen. Virol. 76:1759-1816 (1986); and Petrovskis, E. A., et al., J. Virol. 60:185-193 (1986)) all share a similar pattern of four conserved cysteine residues near their amino termini, the HSV-1 and -2 counterparts carry only two of these (McGeoch, D. J., J. Gen. Virol. 71:2361-2367 (1990); data not shown). It is quite possible that the unique pattern of four conserved cysteines could facilitate the formation of different secondary and tertiary structures which might impart important functional consequences. These might be reflected by findings which show that HSV-1 gE has Fc receptor activity (Johnson, D. C., et al., J. Virol. 62:1347-1354 (1988)), while its PRV and VZV counterparts do not (Edson, C. M., et al., Virology, 161:599-602 (1987); and Zuckerman, F. A., et al., J. Virol. 62:4622-4626 (1988)).

Careful inspection of the N-terminal regions of the MDV gD, gI and gE homologs has revealed that they contain the three basic building blocks of signal peptide sequences a basic, positively charged N-terminal region (n-region) a central hydrophobic region (h-region) , and a more polar terminal region (c-region) that seems to define the cleavage site (von Heijne, G. J. Hol. Biol. 184:99-105 (1985)). Using a recently improved method for predicting signal sequence cleavage sites (von Heijne, G. Nucl. Acids Res. 14: 4683-4690 (1986)), Table 3 shows the likely position of these sites, the location of the hydrophobic transmembrane and charged cytoplasmic domains near the C-terminal end and the location of potential N-glycosylation sites.

Table 3 shows MDV US glycoprotein data on predicted signal peptide cleavage sites and locations of transmembrane and cytoplasmic domains and potential N-glycosylation sites (with respect to the ATG initiation codon).

                  TABLE 3                                                          ______________________________________                                               Predicted  Trans-    Cyto-                                                  Signal Peptide membrane plasmic N-glycosylation                               Name Cleavage Site Domain Domain Sites                                       ______________________________________                                         US6   G.sub.30 -D.sub.31                                                                        358-374   375-403                                                                               87,138,230,306                                 US7 S.sub.18 -I.sub.19 269-288 289-355 147,167,210,245,                            253                                                                        US8 T.sub.18 -A.sub.19 394-419 420-497 60,133,148,203,                             229,277,366,388                                                          ______________________________________                                    

Like the other gI homologs, MDV's counterpart contains a relatively long cytoplasmic domain. However, in contrast to the other gD homologs, MDV gD's signal peptide contains a relatively long n-region (18 residues) , that is unusually highly charged (+4; FIG. 2) considering an overall mean value of +1.7 among eukaryotes, which generally does not vary with length (von Heijne, G, J. Hol. Biol. 184:99-105 (1985)). Although a more distal methionine codon exists directly before the initiation codon (as in the PRV gD homolog, Petrovskis, E. A., et al., J. Virol. 59:216-223 (1986)) the scanning model for translation (Gribskov, M., et al., Proc Natl. Acad. Sci. USA 84:4355-4358 (1987)) favors usage of the more 5'-proximal initiation codon (at position 5964, FIG. 2). Further support is based on an overall translation context that appears at least as good as, if not better than, the one corresponding to the downstream ATG. Despite such a prediction, a possible mRNA cap site location between the two ATG sites, which would preclude such a prediction, cannot be ruled out at this point.

One final point concerning MDV gD requires mention. Using the 10,350 nucleotide DNA sequence as a probe for screening the GenBank (62.0, 12/89) and EMBL (190, 5/89) nucleic acid databases with the computer program FASTA (K-tuple=6), an optimized score of 1027, corresponding to 91.5% nucleotide identity in a 342 bp overlap between MDV gD coding sequences (6479-6814; aa#173-aa#284; FIG. 2) and a previously reported 467 bp MDV DNA segment (Wen, L.-T., et al., J. Virol. 62:3764-3771 (1988)). The latter sequence has been reported to contain a 60 bp segment protected against DNAse digestion by binding of a 28 kD MDV nuclear antigen (MDNA) expressed only in "latently" infected MDV-transformed lymphoblastoid cells. In view of similarities between MDV and VZV, these authors suggested that MDNA may function in a manner analogous to that of EBNA-1 in immortalizing primate cells. In their report, Wen et al. (Wen, L.-T., et al., J. Virol. 62:3764-3771 (1988)) mapped the MDNA binding site to the same EcoRI subfragment of BamHI-A in which MDV gD is located (EcoRI-I, FIG. 1). Although our sequence covering this region is consistent with a complete, uninterrupted ORF containing all the characteristic features of a glycoprotein, and showing significant homology to HSV gD, their sequence contains about 140 bases of 5'-proximal sequence unrelated to any determined from our 5.3 kbp EcoRl-I fragment or its adjoining 3.5 kb sequences. The remaining 327 bp sequence (which contains the putative nuclear antigen binding site) while clearly resembling our gD coding sequence, upon computer translation fails to yield any ORF longer than 30 aa.

Discussion

Recent data have shown that despite MDV's classification as a gammaherpesvirus, based on lymphotropic properties shared with other members of this subfamily, its genome structure (Cebrian, J., et al., Proc. Natl. Acad. Sci. USA 79:555-558 (1982); and Fukuchi, K., et al., J. Virol. 51:102-109 (1984)) and genetic organization of primarily its U_(L) region (Buckmaster, A. E., et al., J. Gen. Virol. 69:2033-2042 (1988)) more closely resembles that of the neurotropic alphaherpesviruses. Moreover, in cases where polypeptide sequences were found conserved among the three herpesvirus subfamilies (e.g. U_(L) genes), significantly higher homology scores were consistently observed against the respective alpha- rather than beta- or gammaherpesvirus counterparts (Davison, A. J., et al., J. Gen. Virol. 67:597-611 (1986); Buckmaster, A. E., et al., J. Gen. Virol. 69:2033-2042 (1988); Ross, L. J. N., et al., J. Gen. Virol. 70:1789-1804 (1989); and Scott, S. D., et al., J. Gen. Virol. 70:3055-3065 (1989)). Alphaherpesvirus S segment genes have previously been found to be unique to members of this taxonomic subfamily (Davison, A. J., et al., J. Gen. Virol. 68:1067-1079 (1987); and Davison, A. J., et al., J. Gen. Virol. 67:597-611 (1986)). The identification of seven MDV homologs of alphaherpesvirus S segment genes in this study is consistent with the idea that MDV shares a closer evolutionary relationship with alphaherpesviruses than gammaherpesviruses. This is further supported by dinucleotide frequency analysis which fails to show a lack of CpG suppression as observed among all gammaherpesviruses thus far studied (Efstathiou, S. et al., J. Gen. Virol. 71:1365-1372 (1990); and Honess, R. W., et al., J. Gen. Virol. 70:837-855 (1989)). The above situation resembles a similar one observed with human herpesvirus-6 (HHV-6), in which case its T-lymphotropism suggested provisional classification as a gammaherpesvirus (Lopez, C., et al., J. Infect. Dis. 157:1271-1273 (1988)). However, subsequent genetic analysis has shown a greater relatedness between HHV-6 and the betaherpesvirus, human cytomegalovirus (HCMV; Lawrence, G. L., et al., J. Virol. 64:287-299 (1990)).

A comparison of the genetic organization of alphaherpesvirus S segment genes is presented in FIG. 4. The organization of these genes in some cases vary greatly in overall length, organization and degree of homology. Nevertheless, the overall gene layouts displayed are consistent with a model to account for the divergence of alphaherpesviruses from a common ancestor by a number of homologous recombination events which result in expansion or contraction of the inverted repeat regions and a concomitant loss or gain of U_(S) gene(s). In the case of VZV, six S segment homologs are lacking compared to HSV-1 (US2, US4, US5, US6, US11, US12). Some genes, such as the US1 homologs, show particular sequence and length divergences Compared to HSV-1 the MDV, VZV and EHV-4 U_(S) 1 homologs lack approximately 120 aa of sequence comparable to the 5'-proximal portion of HSV-1 US1 (alpha 22) Based on Northern blot analysis, S1 nuclease protection analysis and phosphonoacetic acid inhibition studies, in contrast to its relatively uncharacterized immediate-early HSV-1 counterpart, the MDV US1 gene appears to be regulated as an abundantly expressed late class gene (data not shown). In contrast to the other alphaherpesviruses, MDV contains two apparently MDV-specific ORFs. Moreover, the MDV U_(S) region appears to contain approximately 2.6 to 4.0 kb of additional 5'-proximal sequences. Based on a comparison of FIG. 4 and consideration of the expansion-contraction recombination scheme, it appears likely that there are additional MDV-specific U_(S) genes.

Since MDV has long been regarded as a gammaherpesvirus, much of the previous work interpreting their properties has proceeded by analogy with the association between EBV and B cells (Nonoyama, M. p. 333-341. In B. Roizman (ed.), The herpesviruses, vol. 1. Plenum Press (1982); and Wilbur, W. J., et al., Proc. Natl. Acad. Sci. USA 80:726-730 (1983)). Because of a closer genetic relationship to the alphaherpesvirus, and keeping in mind the analysis of HHV-6 above, we agree with Lawrence (1990)) that the lymphotropic properties of MDV and HVT are unlikely to be determined by molecules homologous to EBY and that a delineation of molecular differences between MDV and the neurotropic alphaherpesviruses would be more fruitful in explaining the observed biological differences than employing analogies based on properties of gammaherpesviruses such as EBV and HVS.

To account for such differences, the MDV U_(S) region may be particularly important. With few exceptions, each HSV-1 L component gene possesses an equivalent in VZV (McGeoch, D. J. et al., J. Gen. Virol. 69:1531-1574 (1988)), a considerable number of these are related to beta- and gammaherpesvirus genes as well (29 of 67 EBV counterparts to VZV U_(L) genes; Davison, A. J., et al., J. Gen. Virol. 68:1067-1079 (1987)). In contrasts the S segments of HSV-1 and VZV differ significantly in size and appear to be among the least related parts of the two genomes (Davison, A. J., et al., J. Gen. Virol. 67:597-611 (1986; and Davison, A. J., et al., J. Gen. Virol. 64:1927-1942 (1983)). Recent studies have shown that 11 of 12 open reading frames contained in the HSV-1 S component are dispensable for growth in cell culture (Longnecker, R., et al., Proc. Natl. Acad. Sci. USA 84:4303-4307 (1987); and Weber, P. C., et al., Science 236:576-579 (1987)). The maintenance and evolution of such a dispensable gene cluster suggests the presence of functions relevant to the viruses survival in its specific ecological niche in the natural or laboratory animal host, rather than the presence of functions necessary for replication (Longnecker, R., et al. Proc. Natl. Acad. Sci. USA 84:4303-4307 (1987); and Weber, P. C., et al., Science 236:576-579 (1987)). Consistent with such a hypothesis are findings that HSV mutants carrying different S component gene-specific deletions were significantly less pathogenic and exhibited a reduced capacity for latency establishment in mice (Meignier, B., et al., Virology 162:251-254 (1988)). In regard to the latter, there is evidence suggesting that RNA transcribed from the HSV U_(S) region may be involved in the establishment and maintenance of an in vitro latency system employing human fetus lung fibroblast cells (Scheck, A. C., et al., Intervirology 30:121-136 (1989)). Taken together, the above evidence suggest(s) potentially important role(s) for MDV's U_(S) genes in tissue tropism, latency, and/or induction of cell transformation.

A consideration of the three gD, gI and gE homologs identified in this invention raises two other questions of relevance to future vaccine development. The 11 HSV-1 U_(S) region genes dispensible for growth in tissue culture described above include HSV-1 US7 (gI) and US8 (gE) (Longnecker, R., et al., Proc. Natl. Acad. Sci. USA 84:4303-4307 (1987);, and Weber, P. C., et al., Science 236:576-579 (1987)). Assuming the MDV homologs have the same properties, these genes may be useful as sites for insertion of foreign genes. Further the same two MDV homologs, and especially US8 (gE), may very likely be involved in the pathogenicity-related issues introduced above. Specifically HSV's gE seem to play a role in HSV-lls ability to establish lethal infections and latency in mice (Meignier, B., et al., Virology 162:251-254 (1988)). Further, the gI and gE homologs of PRV of swine play a clear role in PRV virulence for 1-day-old chickens and young pigs (Mettenleiter, Thomas C., et al., Journal of Virology, p. 4030-4032 (December 1987)). Assuming the same holds true for the MDV US7 (gI) and US8 (gE) homologs, it may be possible to inactivate one or both of these genes from very virulent MDV isolates which cause outbreaks not prevented by current vaccines, and thereby creating an attenuated vaccine viruses more closely related to field virus causing disease outbreaks.

A further consideration of the three (gD, gI and gE) homologs identified in this invention raises another interesting question. Fully enveloped infectious MDV virions are only known to be produced in feather follicle epithelial cells (Payne, L. N. p. 347-431. In B. Roizman (ed.), The herpesviruses, vol. 1. Plenum Press (1982)). Because of this, MDV studies have had to rely on limited fibroblast cell cultures which only promote the spread of cell-associated infections in vitro. Over the last 20 years, studies aimed at identifying immunogenic surface antigens have relied on this in vitro culture system and altogether only two glycoprotein antigens (A antigen/gC homolog; B antigen) have been routinely identified and characterized (Binns, M. M., et al., Virus Res. 12:371-382 (1989); Coussens, P. M., et al., J. Virol. 62:2373-2379 (1988); Isfort, R. J., et ale, J. Virol. 59:411-419 (1986); Isfort, R. J., et al., J. Virol. 57:464-474 (1986); and Sithole, I., et al., J. Virol. 62.4270-4279 (1988)). This is despite findings of three MDV gD, gI and gE homologs of the present invention and two additional glycoprotein homologs (gB and gH, Buckmaster, A. E., et al., J. Gen. Virol. 69:2033-2042 (1988); and Ross, L. J. N., et al., J. Gen. Virol, 70:1789-1804 (1989)). While immune chicken sera (ICS) from naturally infected birds is likely to react with many, if not all, MDV-encoded surface antigens, this complex polyclonal sera would only be useful to the extent that antigen expression/processing in semi-productive cell culture resembles that in feather follicle epithelial cells. Northern blot analysis using MDV gD-specific probes suggests that MDV gD MRNA is either not expressed or poorly expressed in DEF cells at a time when extensive cytopathic effects are observed (data not shown). In light of the fact that VZV lacks a gD homolog and is strongly cell-associated, it will be interesting to see whether the -block in MDV virion formation in primary avian fibroblast cells is found to correlate with lack of expression (in these cells) of a glycoprotein, such as gD, and/or some other S component gene(s).

Because the protection against MD conferred by attenuated MDV strains (serotype 2) or HVT (serotype 3) appears to have an immunological basis, there is considerable interest in identifying common antigens. In view of this invention identifying seven MDV U_(S) homologs to U_(S) genes of HSV (the latter of which is clearly less related to MDV than HVT is), it would be surprising if the previous report showing lack of homology between MDV-HVT U_(S) regions (Igarashi, T., et al., Virology 157:351-358 (1987)) were proven correct. Such negative results may reflect the limitations regarding homology estimates based on hybridization, rather than sequence analysis studies.

Example 2 shows the molecular cloning of a construct containing the DNA encoding the complete MDV US7 (gI) gene and part of the MDV US8 (gE) gene. As can be seen, this is accomplished using segments of DNA spanning the gI and part of the gE coding region.

EXAMPLE 2

MOLECULAR CLONING OF A CONSTRUCT CONTAINING THE DNA ENCODING THE COMPLETE MDV US7 (gI) and PART OF MDV US8 (gE)

Construction of a recombinant clone (pKS-MDgI1.59) containing the complete MDV US7 (gI) coding sequence and a portion of the MDV US8 (gE) coding sequence requires two preexisting MDV clones, pKS-MDgD1.75 and p19P1 (FIG. 5). pKS-MDgD1.75 is a recombinant plasmid containing the 1.75 kbp NcoI-SstII subfragment of MDV EcoRl-I ligated into the SmaI-Sst II site of the cloning vector, pBluescript KS-. This clone contains the complete MDV US6 (gD) coding sequence and additional sequences at the 31 end which code for the first 39 amino acids (aa) of MDV gI. p19P1 is a recombinant plasmid containing the 1.5 kbp BamHI-P₁ subfragment of MDV cloned into the unique BamHI site of pUC19. This clone contains the entire MDV gI coding sequence, except for the first 9 aa of its signal sequence. In addition, at the 3' end, p19P1 contains the first 104 aa of the MDV US8 (gE) coding region.

To generate pKS-MDgI1.59, pKS-MgD1.75 is first cut with HincII, which cuts once in the multiple cloning site of the pBluescript vector and once about 180 bp upstream of the insert's SstII terminus. This results in two fragments: one fragment (1.6 kbp) consists primarily of insert sequences encoding MDV US6 (gD); the larger fragment (3.1 kbp) consists of pBluescript vector sequences, in addition to about 180 bp which encode the N-terminus of MDV gI. The 3.1 kb fragment is gel purified and self-ligated by way of the two HincII ends. The resulting recombinant plasmid, pKS-MDgI0.18, is then cut with SstI (in the multiple cloning site, just downstream of the SstII site). Prior to subsequent digestion with SstII, the cohesive SstI ends is made blunt-ended with T4 DNA polymerase. The resulting 301 kbp SstII-SstI (blunt) fragment of pMDgI0.18 is gel purified and used in the final ligation step to create pKS-MDgI1.59. While the enzymatic manipulations of pKS-MDgD1.75 and pKS-MDgI0.18 are taking place, p19P1 is cut with HindIII, which cuts just downstream of the partial MDV US8 (gE) coding sequence in the multiple cloning site of pUC19. Prior to digestion with SstIId, the cohesive HindIII ends is made blunt-ended using Klenow fragment. The smaller SstII-HindIII (blunt) fragment (1.4 kbp) contains a majority of the MDV US7 (gI) coding sequences in addition to 312 nucleotides at the 31 end which code for the 5' end of MDV gE. This 1.4 kbp SstII-HindIII(blunt) fragment is gel purified and ligated to the 3.1 kbp SstII-SstI(blunt) fragment of pKS-MDgD0.18. The resulting recombinant, pKS-MDgI1.59, contains the complete coding sequence for MDV gI and a portion of the N-terminal gE coding sequence. Digestion of pKS-MDgI1.59 with KpnI yields two fragments; the smaller 1.15 kbp fragment contains the complete coding sequence for MDV gI.

Example 3 shows molecular subcloning of a construct containing the complete HDV US8 (gE) gene.

EXAMPLE 3

MOLECULAR CLONING OF A CONSTRUCT ENCODING THE COMPLETE MDV US8 (gE)

Construction of a recombinant clone (p18-MDgE2.53) containing the complete MDV US8 (gE) coding sequence requires a clone other than the BamHI or EcoRl clones used previously GA strain clone GA-02, an EMBL-3 clone containing a partially digested MDV SalI inserts which contains BamHI-A, -Pl, and additional 5' and 3' flanking sequences (kindly provided by P. Sondermeier, Intervet Intl. B. V., Boxmeer, The Netherlands) was used to extend analysis 3' of the EcoRl-I and BamHl-Pl fragments. Smaller SalI subfragments located at the 3' end of this phage clones MDV insert were gel purified and ligated to pUC18 linearized to SalI (pSP18-A, pSP18-B, and pSP18-C, FIG. 1B). The pUC18 subclone, pSP18-A contains the entire MDV US8 (gE) coding sequence and is designated p18-MDgE2.53 for ATCC deposit purposes.

Index of definition of letters in FIG. 2. Table 4 showing the amino acids with both their single letter and three letter symbols.

                  TABLE 4                                                          ______________________________________                                         A     Ala      Alanine     M   Met    Methionine                                 C Cys Cysteine N Asn Asparagine                                                D Asp Aspartic Acid P Pro Proline                                              E Glu Glutamic Acid Q Gln Glutamine                                            F Phe Phenylalanine R Arg Arginine                                             G Gly Glycine S Ser Serine                                                     H His Histidine T Thr Threonine                                                I Ile Isoleucine V Val Valine                                                  K Lys Lysine W Trp Tryptophan                                                  L Leu Leucine Y Tyr Tyrosine                                                 ______________________________________                                    

When the DNA segments encoding glycoproteins gI and gE are altered by insertional, site-directed or deletion mutagenesis, the pathogenicity of the MDV may be reduced. Also, the segments of DNA encoding the non-essential gI and gE can be used as insertion sites for segments of foreign DNA which encode proteins that are antigenically active for the purpose of producing a recombinant vaccine.

ATCC Deposit

The gene for MDV US6 (MDV gD) has been deposited in a plasmid (phagemid) pKS-MDgD1.75, as ATCC 40855, with The American Type Culture Collection, Rockville, Md., 20852, USA.

The gene for MDV US7 (MDV gI) has been deposited in a plasmid (phagemid) pKS-MDgI1.59, as ATCC 75040, with The American Type Culture Collection, Rockville, Md., 20852, USA.

The gene for MDV US8 (MDV gE) has been deposited in a plasmid p18-MDgE 2.53, as ATCC 75039, with The American Type Culture Collection, Rockville, Md., 20852, USA.

Attached are Sequence Listings for Sequence ID NOS. 1, 2 and 3 as previously described in the application.

    __________________________________________________________________________     #             SEQUENCE LISTING                                                    - -  - - (1) GENERAL INFORMATION:                                              - -    (iii) NUMBER OF SEQUENCES:  34                                          - -  - - (2) INFORMATION FOR SEQ ID NO:1:                                      - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH:  10350 b - #ase pairs                                              (B) TYPE:  nucleic a - #cid                                                    (C) STRANDEDNESS:  doub - #le                                                  (D) TOPOLOGY:  linear                                                 - -     (ii) MOLECULE TYPE:  genomic DNA                                       - -    (iii) HYPOTHETICAL:  Yes                                                - -      (v) ANTI-SENSE:  No                                                   - -     (vi) ORIGINAL SOURCE:                                                           (A) ORGANISM:  MDV, - #GA strain                                      - -    (vii) IMMEDIATE SOURCE:                                                          (A) LIBRARY:  genomic                                                 - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #1:                           - - GAATTCCTTG AAATTGGAGT GAAATCTTTA GGGAGGGAGG TTTACCATTG TG -             #GAGAATAT     60                                                                  - - ATAGAGCAAG TAGTACATTA GGGGCTGGGT TAAAGACCAA GTAATTTTTG AC -             #CGGATATC    120                                                                  - - ACGTGATGTA AATTCTAGCA ATTATTGTTC CTAGCAGAAG ATAAAAGCTG GT -             #AGCTATAT    180                                                                  - - AATACAGGCC AAAGTCTCCA AATTACACTT GAGCAGAAAA CCTGCTTTCG GC -             #TCCATCGG    240                                                                  - - AGGCAAC ATG AGT CGT GAT CGA GAT CGA GCC AGA - #CCC GAT ACA CGA TTA           289                                                                                Met Ser Arg Asp Arg Asp - #Arg Ala Arg Pro Asp Thr Arg Leu                      1         - #      5            - #       10                           - - TCA TCG TCA GAT AAT GAG AGC GAC GAC GAA GA - #T TAT CAA CTG CCA CAT           337                                                                        Ser Ser Ser Asp Asn Glu Ser Asp Asp Glu As - #p Tyr Gln Leu Pro His             15                 - # 20                 - # 25                 - # 30        - - TCA CAT CCG GAA TAT GGC AGT GAC TCG TCC GA - #T CAA GAC TTT GAA CTT           385                                                                        Ser His Pro Glu Tyr Gly Ser Asp Ser Ser As - #p Gln Asp Phe Glu Leu                             35 - #                 40 - #                 45               - - AAT AAT GTG GGC AAA TTT TGT CCT CTA CCA TG - #G AAA CCC GAT GTC GCT           433                                                                        Asn Asn Val Gly Lys Phe Cys Pro Leu Pro Tr - #p Lys Pro Asp Val Ala                         50     - #             55     - #             60                   - - CGG TTA TGT GCG GAT ACA AAC AAA CTA TTT CG - #A TGT TTT ATT CGA TGT           481                                                                        Arg Leu Cys Ala Asp Thr Asn Lys Leu Phe Ar - #g Cys Phe Ile Arg Cys                     65         - #         70         - #         75                       - - CGA CTA AAT AGC GGT CCG TTC CAC GAT GCT CT - #T CGG AGA GCA CTA TTC           529                                                                        Arg Leu Asn Ser Gly Pro Phe His Asp Ala Le - #u Arg Arg Ala Leu Phe                 80             - #     85             - #     90                           - - GAT ATT CAT ATG ATT GGT CGA ATG GGA TAT CG - #A CTA AAA CAA GCC GAA           577                                                                        Asp Ile His Met Ile Gly Arg Met Gly Tyr Ar - #g Leu Lys Gln Ala Glu             95                 - #100                 - #105                 - #110        - - TGG GAA ACT ATC ATG AAT TTG ACC CCA CGC CA - #A AGT CTA CAT CTG CGC           625                                                                        Trp Glu Thr Ile Met Asn Leu Thr Pro Arg Gl - #n Ser Leu His Leu Arg                            115  - #               120  - #               125               - - AGG ACT CTG AGG GAT GCT GAT AGT CGA AGC GC - #C CAT CCT ATA TCC GAT           673                                                                        Arg Thr Leu Arg Asp Ala Asp Ser Arg Ser Al - #a His Pro Ile Ser Asp                        130      - #           135      - #           140                   - - ATA TAT GCC TCC GAT AGC ATT TTT CAC CCA AT - #C GCT GCG TCC TCG GGA           721                                                                        Ile Tyr Ala Ser Asp Ser Ile Phe His Pro Il - #e Ala Ala Ser Ser Gly                    145          - #       150          - #       155                       - - ACT ATT TCT TCA GAC TGC GAT GTA AAA GGA AT - #G AAC GAT TTG TCG GTA           769                                                                        Thr Ile Ser Ser Asp Cys Asp Val Lys Gly Me - #t Asn Asp Leu Ser Val                160              - #   165              - #   170                           - - GAC AGT AAA TTG CAT TAA CTATCCAGAC TTGAAGAGAA AG - #CTCTTATT                  817                                                                        Asp Ser Lys Leu His                                                            175                                                                             - - ATATAATTTT AATTGTTAGA CATAGAGCCG ACATTCTTTG ATCTATCTAA TG -              #AGATAAAA    877                                                                  - - TAATAGATTT TGGATTTATT TGTCATGATC TGTTGCAACA AACGCTGACC CC -             #CCCCATCC    937                                                                  - - ATGAAGGGGC GTGTCAAATA ACGTGTTGCC TTTTTGTTGT ATATGAAGAT AT -             #TTAATGTG    997                                                                  - - GCGTTGAGCC TAATGAGAGG AGAACGTGTT TGAATACTGG AGACGAGCGC CG -             #TGTAAGAT   1057                                                                  - - TAAAACATAT TGGAGAGGT  ATG GCC ATG TGG TCT CTA - #CGG CGC AAA TCT            1106                                                                                          - #    Met Ala Met Trp Ser Leu Arg Arg - #Lys Ser                              - #     1             - #  5                - #   10          - - AGC AGG AGT GTG CAA CTC CGG GTA GAT TCT CC - #A AAA GAA CAG AGT TAT          1154                                                                        Ser Arg Ser Val Gln Leu Arg Val Asp Ser Pr - #o Lys Glu Gln Ser Tyr                             15 - #                 20 - #                 25               - - GAT ATA CTT TCT GCC GGC GGG GAA CAT GTT GC - #G CTA TTG CCT AAA TCT          1202                                                                        Asp Ile Leu Ser Ala Gly Gly Glu His Val Al - #a Leu Leu Pro Lys Ser                         30     - #             35     - #             40                   - - GTA CGC AGT CTA GCC AGG ACC ATA TTA ACC GC - #C GCT ACG ATC TCC CAG          1250                                                                        Val Arg Ser Leu Ala Arg Thr Ile Leu Thr Al - #a Ala Thr Ile Ser Gln                    45          - #        50          - #        55                        - - GCT GCT ATG AAA GCT GGA AAA CCA CCA TCG TC - #T CGT TTG TGG GGT GAG          1298                                                                        Ala Ala Met Lys Ala Gly Lys Pro Pro Ser Se - #r Arg Leu Trp Gly Glu                 60             - #     65             - #     70                           - - ATA TTC GAC AGA ATG ACT GTC ACG CTT AAC GA - #A TAT GAT ATT TCT GCT          1346                                                                        Ile Phe Asp Arg Met Thr Val Thr Leu Asn Gl - #u Tyr Asp Ile Ser Ala             75                 - # 80                 - # 85                 - # 90        - - TCG CCA TTC CAC CCG ACA GAC CCG ACG AGA AA - #A ATT GTA GGC CGG GCT          1394                                                                        Ser Pro Phe His Pro Thr Asp Pro Thr Arg Ly - #s Ile Val Gly Arg Ala                             95 - #                100 - #                105               - - TTA CGG TGT ATT GAA CGT GCT CCT CTT ACA CA - #C GAA GAA ATG GAC ACT          1442                                                                        Leu Arg Cys Ile Glu Arg Ala Pro Leu Thr Hi - #s Glu Glu Met Asp Thr                        110      - #           115      - #           120                   - - CGG TTT ACT ATC ATG ATG TAT TGG TGT TGT CT - #T GGA CAT GCT GGA TAC          1490                                                                        Arg Phe Thr Ile Met Met Tyr Trp Cys Cys Le - #u Gly His Ala Gly Tyr                    125          - #       130          - #       135                       - - TGT ACT GTT TCG CGC TTA TAT GAG AAG AAT GT - #C CGT CTT ATG GAC ATA          1538                                                                        Cys Thr Val Ser Arg Leu Tyr Glu Lys Asn Va - #l Arg Leu Met Asp Ile                140              - #   145              - #   150                           - - GTA GGT TCG GCA ACG GGC TGT GGA ATA AGT CC - #A CTC CCC GAA ATA GAG          1586                                                                        Val Gly Ser Ala Thr Gly Cys Gly Ile Ser Pr - #o Leu Pro Glu Ile Glu            155                 1 - #60                 1 - #65                 1 -       #70                                                                               - - TCT TAT TGG AAA CCT TTA TGT CGT GCC GTC GC - #T ACT AAG GGG AAT         GCA     1634                                                                     Ser Tyr Trp Lys Pro Leu Cys Arg Ala Val Al - #a Thr Lys Gly Asn Ala                           175  - #               180  - #               185               - - GCA ATC GGT GAT GAT GCT GAA TTG GCA CAT TA - #T CTG ACA AAT CTT CGG          1682                                                                        Ala Ile Gly Asp Asp Ala Glu Leu Ala His Ty - #r Leu Thr Asn Leu Arg                        190      - #           195      - #           200                   - - GAA TCG CCA ACA GGA GAC GGG GAA TCC TAC TT - #A TAA CTAATCGCAC               1728                                                                        Glu Ser Pro Thr Gly Asp Gly Glu Ser Tyr Le - #u                                        205          - #       210                                              - - AATTATTAAT AGGATTTTAG GAAAAACTGC TACTAACGTT GTTTAAATAA TA -              #AAATTTTA   1788                                                                  - - TTTTCAATAA GGCATTACAG TGTTGTCATG ATTGTATGTA TTATATGGGG TA -             #TGCATGAG   1848                                                                  - - GATTACTTCG ATTGAAACTT TGTCTAAATG TCTGTAGGAT TTTACTATTC AT -             #TAGTCTGG   1908                                                                  - - ATCGAGGCGG ACGTAAATGG AGATTGCGGC AAATGTAGGG GTGCTGGTAC AT -             #AAGACCTC   1968                                                                  - - CAACATCCAT TCGACTCATC GGCCTGCGTC CAAATGGATA TGTTGATGTA CC -             #TTGTAAAG   2028                                                                  - - TTATGACATT AGAAGATCGA TGGTGAATAG TGGGATCTAT ATCCATGCTA TT -             #CTCAATAT   2088                                                                  - - TGCATGATAT GCAATGTTCC CGGTTAGGTT TGATAAGATC ATGTATGGTT CT -             #ATAATACA   2148                                                                  - - ACTCCTCTTC AGAAGAATCA TTTATTTTAT GTCCACTGTC CTTGGATATT CC -             #AGTTTCTG   2208                                                                  - - TCAATCGATT CGCTTGCATT TGCGTGCAGC ATGTCTTGAT GGCATTTCCT AT -             #GCTATCAT   2268                                                                  - - CCGGCAGGCC TAAGGGTGTT CTATACTCGC ACACAGGTAG AGCAAGAACC AC -             #GGCATATC   2328                                                                  - - GAGCTACCTC TATTGCCCCG CTAAGGACAT TTCTTGCAGA CTGTATTGTC AT -             #GAACATAT   2388                                                                  - - TTCGTGTATT GTGTCGATCA TAACCCTTGT TGATTCCTAT GGAAAGCATT GT -             #GGTCCAGT   2448                                                                  - - TTTCCAGATG AAATGAAAAC AATGCGGGCA AAAATGGTCC CACCTGTTTC AT -             #CTTCAATG   2508                                                                  - - CATCTCTCAC ATCCCAAGTT CTATAGAATA TTCTCCACTG ACCAGTTTCG GT -             #AAGATCAG   2568                                                                  - - TTTCTGTAAA ATTTGTGATA GTTTCAATCG AAAACATTTT GTCCATCATG GC -             #AAAAAATC   2628                                                                  - - TATAGGCAGA CCAGATAACC ATTTGACACC ACATATCCTT GTGTATATCA AA -             #CGATGTAA   2688                                                                  - - TAGATCCCTC GTTAGTAGAT ATGGTACATA AAAGGCCTAA TCTCTCTCGG GC -             #TTCCATAC   2748                                                                  - - ATTGAACGAT TCCTTCTGTG AATTCATCAA CAACCACATG CCAAAAATTT AC -             #ATTAGTAA   2808                                                                  - - TCTTTCTCGG TGGCTTACCA AATCGTCCTC TTGGTATATC CATATCATCG AA -             #CATTGTAG   2868                                                                  - - CATTGACTCT GCTCATCGTT GTCTTTCAAA TGCGCTCGAT TGTTGAATCT CT -             #CCTGATGT   2928                                                                  - - TAGAAGTATA TGGAAGATAG CCTGGATACA TAAGTGATCT AGAAGGGTTT GT -             #TATTGCAC   2988                                                                  - - TAATATACAA ATTATACGTG ACACTATAGC GACGGTTGTA GCGATGCACC TA -             #ATCGTAAT   3048                                                                  - - GTGTATACGC CCCATCATGT AATTATATCT AATTGGTAGC AAGTAGGTCT GT -             #CGAATAAC   3108                                                                  - - AGCTAATGAC TACCGGCTCT ACATTTTTTC TGTATTCGTG ACTTTCCTGT CG -             #CAGTGTAA   3168                                                                  - - CGAACCGGAA TTGCAATCGC ATCTCTATCT TCTTTCTTGC AACATTTTCC AC -             #AACAGAAT   3228                                                                  - - AATCTGCCGG GTGTACTACT CATTTGAGGT GGTTCGATTT CCGGAGGTTT TA -             #GAGGATTG   3288                                                                  - - GGTGGGGACC CGAGGATTTT GTATACACAT ACCATATCAC TGTCGCAAAA AT -             #GCGCTCTA   3348                                                                  - - TCTTCTGGGG TGTCGAACTT CGGTTCCCAT GTAGATGTCA AGAGAGTTTG AA -             #TATTGTCG   3408                                                                  - - GGAATGGCCC ACGGCATACC GGACCAGGTC CCAGACACTT TGATTGCAAG TA -             #ACCTTTTT   3468                                                                  - - GGCAAAGGAA TACATTCGAG CGCAATGGCA CATATATCTG CCGCCCCAAC TA -             #TCCACAAG   3528                                                                  - - CTATGTGGAG CATTACCAGA AACTTCAGAT TCCAACATCA AATATCCAGA TA -             #GAACATCC   3588                                                                  - - TGCCATTCTG TGGAACATCC TGCAACATCT TCAAATAGCC GCACTATAAA CG -             #AATCCCTA   3648                                                                  - - GTTCCGGCCA ATCCGGTACC ACGAACTCCA GTTCCATCTG GTGGCTTTGT CC -             #TTACTATC   3708                                                                  - - GGTCGATGTT GCCGAGGAAG AATTAACATG GGTTTGGCAA AACGGAATAG GT -             #CTGCAGCT   3768                                                                  - - CTGGCGATTA TGGGCACACC CACATCATCC TGTATTTGTT CCATACATTG CT -             #TTATAAGG   3828                                                                  - - AATATCCATA AAGTAGATGC AGCATCTCTA GATCTTCCTG GCAATCGATC GC -             #ATTCATCT   3888                                                                  - - AGAAGTGTGA CTATAGTTAT CATGGACACA CCCATCTTCA CCTCCACCAA TA -             #ATCTTTTT   3948                                                                  - - TATTGTTAAT AACTGGGCCG GTCTGATCTC CAAATCTTAT ACTCTGGTAG AA -             #TATGAAAC   4008                                                                  - - AGGGTTAAAA CTAGGTAATA GACTGGATGT CTTCGACTCC GGAGGCAGAA AC - #G          ATG     4064                                                                                       - #                  - #                  - #              Met                                                                                                - #                  - #                  - #       1        - - GAA TGT GGC ATT TCT TCG TCG AAA GTA CAC GA - #C TCT AAA ACT AAT ACT          4112                                                                        Glu Cys Gly Ile Ser Ser Ser Lys Val His As - #p Ser Lys Thr Asn Thr                         5     - #              10    - #              15                   - - ACC TAC GGA ATT ATA CAT AAC AGC ATC AAT GG - #T ACG GAT ACG ACG TTG          4160                                                                        Thr Tyr Gly Ile Ile His Asn Ser Ile Asn Gl - #y Thr Asp Thr Thr Leu                     20         - #         25         - #         30                       - - TTT GAT ACT TTT CCC GAC AGT ACC GAT AAC GC - #G GAA GTG ACG GGG GAT          4208                                                                        Phe Asp Thr Phe Pro Asp Ser Thr Asp Asn Al - #a Glu Val Thr Gly Asp                 35             - #     40             - #     45                           - - GTG GAC GAT GTG AAG ACT GAG AGC TCT CCC GA - #G TCC CAA TCT GAA GAT          4256                                                                        Val Asp Asp Val Lys Thr Glu Ser Ser Pro Gl - #u Ser Gln Ser Glu Asp             50                 - # 55                 - # 60                 - # 65        - - TTG TCA CCT TTT GGG AAC GAT GGA AAT GAA TC - #C CCC GAA ACG GTG ACG          4304                                                                        Leu Ser Pro Phe Gly Asn Asp Gly Asn Glu Se - #r Pro Glu Thr Val Thr                             70 - #                 75 - #                 80               - - GAC ATT GAT GCA GTT TCA GCT GTG CGA ATG CA - #G TAT AAC ATT GTT TCA          4352                                                                        Asp Ile Asp Ala Val Ser Ala Val Arg Met Gl - #n Tyr Asn Ile Val Ser                         85     - #             90     - #             95                   - - TCG TTA CCG CCC GGA TCT GAA GGG TAT ATC TA - #T GTT TGT ACA AAG CGT          4400                                                                        Ser Leu Pro Pro Gly Ser Glu Gly Tyr Ile Ty - #r Val Cys Thr Lys Arg                    100          - #       105          - #       110                       - - GGG GAT AAT ACC AAG AGA AAA GTC ATT GTG AA - #A GCT GTG ACT GGT GGC          4448                                                                        Gly Asp Asn Thr Lys Arg Lys Val Ile Val Ly - #s Ala Val Thr Gly Gly                115              - #   120              - #   125                           - - AAA ACC CTT GGG AGT GAA ATT GAT ATA TTA AA - #A AAA ATG TCT CAC CGC          4496                                                                        Lys Thr Leu Gly Ser Glu Ile Asp Ile Leu Ly - #s Lys Met Ser His Arg            130                 1 - #35                 1 - #40                 1 -       #45                                                                               - - TCC ATA ATT AGA TTA GTT CAT GCT TAT AGA TG - #G AAA TCG ACA GTT         TGT     4544                                                                     Ser Ile Ile Arg Leu Val His Ala Tyr Arg Tr - #p Lys Ser Thr Val Cys                           150  - #               155  - #               160               - - ATG GTA ATG CCT AAA TAC AAA TGC GAC TTG TT - #T ACG TAC ATA GAT ATC          4592                                                                        Met Val Met Pro Lys Tyr Lys Cys Asp Leu Ph - #e Thr Tyr Ile Asp Ile                        165      - #           170      - #           175                   - - ATG GGA CCA TTG CCA CTA AAT CAA ATA ATT AC - #G ATA GAA CGG GGT TTG          4640                                                                        Met Gly Pro Leu Pro Leu Asn Gln Ile Ile Th - #r Ile Glu Arg Gly Leu                    180          - #       185          - #       190                       - - CTT GGA GCA TTG GCA TAT ATC CAC GAA AAG GG - #T ATA ATA CAT CGT GAT          4688                                                                        Leu Gly Ala Leu Ala Tyr Ile His Glu Lys Gl - #y Ile Ile His Arg Asp                195              - #   200              - #   205                           - - GTA AAA ACT GAA AAT ATA TTT TTG GAT AAA CC - #T GAA AAT GTA GTA TTG          4736                                                                        Val Lys Thr Glu Asn Ile Phe Leu Asp Lys Pr - #o Glu Asn Val Val Leu            210                 2 - #15                 2 - #20                 2 -       #25                                                                               - - GGG GAC TTT GGG GCA GCA TGT AAA TTA GAT GA - #A CAT ACA GAT AAA         CCC     4784                                                                     Gly Asp Phe Gly Ala Ala Cys Lys Leu Asp Gl - #u His Thr Asp Lys Pro                           230  - #               235  - #               240               - - AAA TGT TAT GGA TGG AGT GGA ACT CTG GAA AC - #C AAT TCG CCT GAA CTG          4832                                                                        Lys Cys Tyr Gly Trp Ser Gly Thr Leu Glu Th - #r Asn Ser Pro Glu Leu                        245      - #           250      - #           255                   - - CTT GCA CTT GAT CCA TAC TGT ACA AAA ACT GA - #T ATA TGG AGT GCA GGA          4880                                                                        Leu Ala Leu Asp Pro Tyr Cys Thr Lys Thr As - #p Ile Trp Ser Ala Gly                    260          - #       265          - #       270                       - - TTA GTT CTG TTT GAG ATG TCA GTA AAA AAT AT - #A ACC TTT TTT GGC AAA          4928                                                                        Leu Val Leu Phe Glu Met Ser Val Lys Asn Il - #e Thr Phe Phe Gly Lys                275              - #   280              - #   285                           - - CAA GTA AAC GGC TCA GGT TCT CAG CTG AGA TC - #C ATA ATT AGA TGC CTG          4976                                                                        Gln Val Asn Gly Ser Gly Ser Gln Leu Arg Se - #r Ile Ile Arg Cys Leu            290                 2 - #95                 3 - #00                 3 -       #05                                                                               - - CAA GTC CAT CCG TTG GAA TTT CCA CAG AAC AA - #T TCT ACA AAC TTA         TGC     5024                                                                     Gln Val His Pro Leu Glu Phe Pro Gln Asn As - #n Ser Thr Asn Leu Cys                           310  - #               315  - #               320               - - AAA CAC TTC AAG CAG TAC GCG ATT CAG TTA CG - #A CAT CCA TAT GCA ATC          5072                                                                        Lys His Phe Lys Gln Tyr Ala Ile Gln Leu Ar - #g His Pro Tyr Ala Ile                        325      - #           330      - #           335                   - - CCT CAG ATT ATA CGA AAG AGT GGT ATG ACG AT - #G GAT CTT GAA TAT GCT          5120                                                                        Pro Gln Ile Ile Arg Lys Ser Gly Met Thr Me - #t Asp Leu Glu Tyr Ala                    340          - #      345           - #      350                        - - ATT GCA AAA ATG CTC ACA TTC GAT CAG GAG TT - #T AGA CCA TCT GCC CAA          5168                                                                        Ile Ala Lys Met Leu Thr Phe Asp Gln Glu Ph - #e Arg Pro Ser Ala Gln                355              - #   360              - #   365                           - - GAT ATT TTA ATG TTG CCT CTT TTT ACT AAA GA - #A CCC GCT GAC GCA TTA          5216                                                                        Asp Ile Leu Met Leu Pro Leu Phe Thr Lys Gl - #u Pro Ala Asp Ala Leu            370                 3 - #75                 3 - #80                 3 -       #85                                                                               - - TAC ACG ATA ACT GCC GCT CAT ATG TAA ACACCCGTC - #A AAAATAACTT                5263                                                                       Tyr Thr Ile Thr Ala Ala His Met                                                                390                                                             - - CAATGATTCA TTTTATAATA TATACTACGC GTTACCTGCA ATAATGACAA CA -              #TTCGAAGT   5323                                                                  - - CTTTGAAGAT TCGCAGACCT TTTTTGCGA ATG GCA CCT TCG GGA - # CCT ACG         CCA     5376                                                                                       - #              Met Ala P - #ro Ser Gly Pro Thr Pro                          - #               1   - #            5                        - - TAT TCC CAC AGA CCG CAA ATA AAG CAT TAT GG - #A ACA TTT TCG GAT TGC          5424                                                                        Tyr Ser His Arg Pro Gln Ile Lys His Tyr Gl - #y Thr Phe Ser Asp Cys                 10             - #     15             - #     20                           - - ATG AGA TAT ACT CTA AAC GAT GAG AGT AAG GT - #A GAT GAT AGA TGT TCA          5472                                                                        Met Arg Tyr Thr Leu Asn Asp Glu Ser Lys Va - #l Asp Asp Arg Cys Ser             25                 - # 30                 - # 35                 - # 40        - - GAC ATA CAT AAC TCC TTA GCA CAA TCC AAT GT - #T ACT TCA AGC ATG TCT          5520                                                                        Asp Ile His Asn Ser Leu Ala Gln Ser Asn Va - #l Thr Ser Ser Met Ser                             45 - #                 50 - #                 55               - - GTA ATG AAC GAT TCG GAA GAA TGT CCA TTA AT - #A AAT GGA CCT TCG ATG          5568                                                                        Val Met Asn Asp Ser Glu Glu Cys Pro Leu Il - #e Asn Gly Pro Ser Met                         60     - #             65     - #             70                   - - CAG GCA GAG GAC CCT AAA AGT GTT TTT TAT AA - #A GTT CGT AAG CCT GAC          5616                                                                        Gln Ala Glu Asp Pro Lys Ser Val Phe Tyr Ly - #s Val Arg Lys Pro Asp                     75         - #         80         - #         85                       - - CGA AGT CGT GAT TTT TCA TGG CAA AAT CTG AA - #C TCC CAT GGC AAT AGT          5664                                                                        Arg Ser Arg Asp Phe Ser Trp Gln Asn Leu As - #n Ser His Gly Asn Ser                 90             - #     95             - #    100                           - - GGT CTA CGT CGT GAA AAA TAT ATA CGT TCC TC - #T AAG AGG CGA TGG AAG          5712                                                                        Gly Leu Arg Arg Glu Lys Tyr Ile Arg Ser Se - #r Lys Arg Arg Trp Lys            105                 1 - #10                 1 - #15                 1 -       #20                                                                               - - AAT CCC GAG ATA TTT AAG GTA TCT TTG AAA TG - #T GAA TCA ATT GGC         GCT     5760                                                                     Asn Pro Glu Ile Phe Lys Val Ser Leu Lys Cy - #s Glu Ser Ile Gly Ala                           125  - #               130  - #               135               - - GGT AAC GGA ATA AAA ATT TCA TTC TCA TTT TT - #C TAA CATTATAATA               5806                                                                        Gly Asn Gly Ile Lys Ile Ser Phe Ser Phe Ph - #e                                            140      - #           145                                          - - TATCAGATCG TTTCTTATAT ACTTATTTTC ATCGTCGGGA TATGACTAAC GT -              #ATACTAAG   5866                                                                  - - TTACAAGAAA CAACTGCTTA ACGTCGAACA TAACGGAAAT AAAAATATAT AT -             #AGCGTCTC   5926                                                                  - - CTATAACTGT TATATTGGCA CCTTTTAGAG CTTCGGT ATG AAT AGA - #TAC AGA         TAT    5981                                                                                        - #                  - #     Met Asn Arg Tyr Arg Tyr                          - #                  - #     -30            - #             -25                                                                               - - GAA AGT ATT TTT TTT AGA TAT ATC TCA TCC AC - #G AGA ATG ATT CTT         ATA     6029                                                                     Glu Ser Ile Phe Phe Arg Tyr Ile Ser Ser Th - #r Arg Met Ile Leu Ile                           -20  - #               -15  - #               -10               - - ATC TGT TTA CTT TTG GGA ACT GGG GAC ATG TC - #C GCA ATG GGA CTT AAG          6077                                                                        Ile Cys Leu Leu Leu Gly Thr Gly Asp Met Se - #r Ala Met Gly Leu Lys                         -5     - #             1     - #          5                        - - AAA GAC AAT TCT CCG ATC ATT CCC ACA TTA CA - #T CCG AAA GGT AAT GAA          6125                                                                        Lys Asp Asn Ser Pro Ile Ile Pro Thr Leu Hi - #s Pro Lys Gly Asn Glu                 10             - #     15             - #     20                           - - AAC CTC CGG GCT ACT CTC AAT GAA TAC AAA AT - #C CCG TCT CCA CTG TTT          6173                                                                        Asn Leu Arg Ala Thr Leu Asn Glu Tyr Lys Il - #e Pro Ser Pro Leu Phe             25                 - # 30                 - # 35                 - # 40        - - GAT ACA CTT GAC AAT TCA TAT GAG ACA AAA CA - #C GTA ATA TAT ACG GAT          6221                                                                        Asp Thr Leu Asp Asn Ser Tyr Glu Thr Lys Hi - #s Val Ile Tyr Thr Asp                             45 - #                 50 - #                 55               - - AAT TGT AGT TTT GCT GTT TTG AAT CCA TTT GG - #C GAT CCG AAA TAT ACG          6269                                                                        Asn Cys Ser Phe Ala Val Leu Asn Pro Phe Gl - #y Asp Pro Lys Tyr Thr                         60     - #             65     - #             70                   - - CTT CTC AGT TTA CTG TTG ATG GGA CGA CGC AA - #A TAT GAT GCT CTA GTA          6317                                                                        Leu Leu Ser Leu Leu Leu Met Gly Arg Arg Ly - #s Tyr Asp Ala Leu Val                     75         - #         80         - #         85                       - - GCA TGG TTT GTC TTG GGC AGA GCA TGT GGG AG - #A CCA ATT TAT TTA CGT          6365                                                                        Ala Trp Phe Val Leu Gly Arg Ala Cys Gly Ar - #g Pro Ile Tyr Leu Arg                 90             - #     95             - #    100                           - - GAA TAT GCC AAC TGC TCT ACT AAT GAA CCA TT - #T GGA ACT TGT AAA TTA          6413                                                                        Glu Tyr Ala Asn Cys Ser Thr Asn Glu Pro Ph - #e Gly Thr Cys Lys Leu            105                110 - #                 115 - #                 120          - - AAG TCC CTA GGA TGG TGG GAT AGA AGA TAT GC - #A ATG ACG AGT TAT ATC          6461                                                                        Lys Ser Leu Gly Trp Trp Asp Arg Arg Tyr Al - #a Met Thr Ser Tyr Ile                            125  - #               130  - #               135               - - GAT CGA GAT GAA TTG AAA TTG ATT ATT GCA GC - #A CCC AGT CGT GAG CTA          6509                                                                        Asp Arg Asp Glu Leu Lys Leu Ile Ile Ala Al - #a Pro Ser Arg Glu Leu                        140      - #           145      - #           150                   - - AGT GGA TTA TAT ACG CGT TTA ATA ATT ATT AA - #T GGA GAA CCC ATT TCG          6557                                                                        Ser Gly Leu Tyr Thr Arg Leu Ile Ile Ile As - #n Gly Glu Pro Ile Ser                    155          - #       160          - #       165                       - - AGT GAC ATA TTA CTG ACT GTT AAA GGA ACA TG - #T AGT TTT TCG AGA CGG          6605                                                                        Ser Asp Ile Leu Leu Thr Val Lys Gly Thr Cy - #s Ser Phe Ser Arg Arg                170              - #   175              - #   180                           - - GGG ATA AAG GAT AAC AAA CTA TGC AAA CCG TT - #C AGT TTT TTT GTC AAT          6653                                                                        Gly Ile Lys Asp Asn Lys Leu Cys Lys Pro Ph - #e Ser Phe Phe Val Asn            185                 1 - #90                 1 - #95                 2 -       #00                                                                               - - GGT ACA ACA CGG CTG TTA GAC ATG GTG CGA AC - #A GGA ACC CCG AGA         GCC     6701                                                                     Gly Thr Thr Arg Leu Leu Asp Met Val Arg Th - #r Gly Thr Pro Arg Ala                           205  - #               210  - #               215               - - CAT GAA GAA AAT GTG AAG CAG TGG CTT GAA CG - #A AAT GGT GGT AAA CAT          6749                                                                        His Glu Glu Asn Val Lys Gln Trp Leu Glu Ar - #g Asn Gly Gly Lys His                        220      - #           225      - #           230                   - - CTA CCA ATC GTC GTC GAA ACA TCT ATG CAA CA - #A GTC TCA AAT TTG CCG          6797                                                                        Leu Pro Ile Val Val Glu Thr Ser Met Gln Gl - #n Val Ser Asn Leu Pro                    235          - #       240          - #       245                       - - AGA AGT TTT AGA GAT TCA TAT TTA AAA TCA CC - #T GAC GAC GAT AAA TAT          6845                                                                        Arg Ser Phe Arg Asp Ser Tyr Leu Lys Ser Pr - #o Asp Asp Asp Lys Tyr                250              - #   255              - #   260                           - - AAT GAC GTC AAA ATG ACA TCG GCC ACT ACT AA - #T AAC ATT ACC ACC TCC          6893                                                                        Asn Asp Val Lys Met Thr Ser Ala Thr Thr As - #n Asn Ile Thr Thr Ser            265                 2 - #70                 2 - #75                 2 -       #80                                                                               - - GTG GAT GGT TAC ACT GGA CTC ACT AAT CGG CC - #C GAG GAC TTT GAG         AAA     6941                                                                     Val Asp Gly Tyr Thr Gly Leu Thr Asn Arg Pr - #o Glu Asp Phe Glu Lys                           285  - #               290  - #               295               - - GCA CCA TAC ATA ACT AAA CGA CCG ATA ATC TC - #T GTC GAG GAG GCA TCC          6989                                                                        Ala Pro Tyr Ile Thr Lys Arg Pro Ile Ile Se - #r Val Glu Glu Ala Ser                        300      - #           305      - #           310                   - - AGT CAA TCA CCT AAA ATA TCA ACA GAA AAA AA - #A TCC CGA ACG CAA ATA          7037                                                                        Ser Gln Ser Pro Lys Ile Ser Thr Glu Lys Ly - #s Ser Arg Thr Gln Ile                    315          - #       320          - #       325                       - - ATA ATT TCA CTA GTT GTT CTA TGC GTC ATG TT - #T TGT TTC ATT GTA ATC          7085                                                                        Ile Ile Ser Leu Val Val Leu Cys Val Met Ph - #e Cys Phe Ile Val Ile                330              - #   335              - #   340                           - - GGG TCT GGT ATA TGG ATC CTT CGC AAA CAC CG - #C AAA ACG GTG ATG TAT          7133                                                                        Gly Ser Gly Ile Trp Ile Leu Arg Lys His Ar - #g Lys Thr Val Met Tyr            345                 3 - #50                 3 - #55                 3 -       #60                                                                               - - GAT AGA CGT CGT CCA TCA AGA CGG GCA TAT TC - #C CGC CTA TAA                  - #7175                                                                    Asp Arg Arg Arg Pro Ser Arg Arg Ala Tyr Se - #r Arg Leu                                        365  - #               370                                      - - CACGTGTTTG GTATGGGCGT GTCGCTATAG TGCATAAGAA GTTGACTACA TT -              #GATCAATG   7235                                                                  - - ACATTATATA GCTTCTTTGG TCAGATAGAC GGCGTGTGTG ATTGCG ATG - #TAT GTA           7290                                                                                          - #                  - #               Met Tyr - #Val        CTA CAA TTA TTA TTT TGG ATC CGC CTC TTT CG - #A GGC ATC TGG TCT ATA           7338                                                                             Leu Gln Leu Leu Phe Trp Ile Arg Leu Phe Ar - #g Gly Ile Trp Ser Ile          15                 - - #10                  - #-5                  - #1          - - GTT TAT ACT GGA ACA TCT GTT ACG TTA TCA AC - #G GAC CAA TCT GCT CTT          7386                                                                        Val Tyr Thr Gly Thr Ser Val Thr Leu Ser Th - #r Asp Gln Ser Ala Leu                         5     - #              10    - #              15                   - - GTT GCG TTC CGC GGA TTA GAT AAA ATG GTG AA - #T GTA CGC GGC CAA CTT          7434                                                                        Val Ala Phe Arg Gly Leu Asp Lys Met Val As - #n Val Arg Gly Gln Leu                     20         - #         25         - #         30                       - - TTA TTC CTG GGC GAC CAG ACT CGG ACC AGT TC - #T TAT ACA GGA ACG ACG          7482                                                                        Leu Phe Leu Gly Asp Gln Thr Arg Thr Ser Se - #r Tyr Thr Gly Thr Thr                 35             - #     40             - #     45                           - - GAA ATC TTG AAA TGG GAT GAA GAA TAT AAA TG - #C TAT TCC GTT CTA CAT          7530                                                                        Glu Ile Leu Lys Trp Asp Glu Glu Tyr Lys Cy - #s Tyr Ser Val Leu His             50                 - # 55                 - # 60                 - # 65        - - GCG ACA TCA TAT ATG GAT TGT CCT GCT ATA GA - #C GCC ACG GTA TTC AGA          7578                                                                        Ala Thr Ser Tyr Met Asp Cys Pro Ala Ile As - #p Ala Thr Val Phe Arg                             70 - #                 75 - #                 80               - - GGC TGT AGA GAC GCT GTG GTA TAT GCT CAA CC - #T CAT GGT AGA GTA CAA          7626                                                                        Gly Cys Arg Asp Ala Val Val Tyr Ala Gln Pr - #o His Gly Arg Val Gln                         85     - #             90     - #             95                   - - CCT TTT CCC GAA AAG GGA ACA TTG TTG AGA AT - #T GTC GAA CCC AGA GTA          7674                                                                        Pro Phe Pro Glu Lys Gly Thr Leu Leu Arg Il - #e Val Glu Pro Arg Val                    100          - #       105          - #       110                       - - TCA GAT ACA GGC AGC TAT TAC ATA CGT GTA TC - #T CTC GCT GGA AGA AAT          7722                                                                        Ser Asp Thr Gly Ser Tyr Tyr Ile Arg Val Se - #r Leu Ala Gly Arg Asn                115              - #   120              - #   125                           - - ATG AGC GAT ATA TTT AGA ATG GTT GTT ATT AT - #A AGG AGT AGC AAA TCT          7770                                                                        Met Ser Asp Ile Phe Arg Met Val Val Ile Il - #e Arg Ser Ser Lys Ser            130                 1 - #35                 1 - #40                 1 -       #45                                                                               - - TGG GCC TGT AAT CAC TCT GCT AGT TCA TTT CA - #G GCC CAT AAA TGT         ATT     7818                                                                     Trp Ala Cys Asn His Ser Ala Ser Ser Phe Gl - #n Ala His Lys Cys Ile                           150  - #               155  - #               160               - - CGC TAT GTC GAC CGT ATG GCC TTT GAA AAT TA - #T CTG ATT GGA CAT GTA          7866                                                                        Arg Tyr Val Asp Arg Met Ala Phe Glu Asn Ty - #r Leu Ile Gly His Val                        165      - #           170      - #           175                   - - GGC AAT TTG CTG GAC AGT GAC TCG GAA TTG CA - #T GCA ATT TAT AAT ATT          7914                                                                        Gly Asn Leu Leu Asp Ser Asp Ser Glu Leu Hi - #s Ala Ile Tyr Asn Ile                    180          - #       185          - #       190                       - - ACT CCC CAA TCC ATT TCC ACA GAT ATT AAT AT - #T GTA ACG ACT CCA TTT          7962                                                                        Thr Pro Gln Ser Ile Ser Thr Asp Ile Asn Il - #e Val Thr Thr Pro Phe                195              - #   200              - #   205                           - - TAC GAT AAT TCG GGA ACA ATT TAT TCA CCT AC - #G GTT TTT AAT TTG TTT          8010                                                                        Tyr Asp Asn Ser Gly Thr Ile Tyr Ser Pro Th - #r Val Phe Asn Leu Phe            210                 2 - #15                 2 - #20                 2 -       #25                                                                               - - AAT AAC AAT TCC CAT GTC GAT GCA ATG AAT TC - #G ACT GGT ATG TGG         AAT     8058                                                                     Asn Asn Asn Ser His Val Asp Ala Met Asn Se - #r Thr Gly Met Trp Asn                           230  - #               235  - #               240               - - ACC GTT TTA AAA TAT ACC CTT CCA AGG CTT AT - #T TAC TTT TCT ACG ATG          8106                                                                        Thr Val Leu Lys Tyr Thr Leu Pro Arg Leu Il - #e Tyr Phe Ser Thr Met                        245      - #           250      - #           255                   - - ATT GTA CTA TGT ATA ATA GCA TTG GCA ATT TA - #T TTG GTC TGT GAA AGG          8154                                                                        Ile Val Leu Cys Ile Ile Ala Leu Ala Ile Ty - #r Leu Val Cys Glu Arg                    260          - #       265          - #       270                       - - TGC CGC TCT CCC CAT CGT AGG ATA TAC ATC GG - #T GAA CCA AGA TCT GAT          8202                                                                        Cys Arg Ser Pro His Arg Arg Ile Tyr Ile Gl - #y Glu Pro Arg Ser Asp                275              - #   280              - #   285                           - - GAG GCC CCA CTC ATC ACT TCT GCA GTT AAC GA - #A TCA TTT CAA TAT GAT          8250                                                                        Glu Ala Pro Leu Ile Thr Ser Ala Val Asn Gl - #u Ser Phe Gln Tyr Asp            290                 2 - #95                 3 - #00                 3 -       #05                                                                               - - TAT AAT GTA AAG GAA ACT CCT TCA GAT GTT AT - #T GAA AAG GAG TTG         ATG     8298                                                                     Tyr Asn Val Lys Glu Thr Pro Ser Asp Val Il - #e Glu Lys Glu Leu Met                           310  - #               315  - #               320               - - GAA AAA CTG AAG AAG AAA GTC GAA TTG TTG GA - #A AGA GAA GAA TGT GTA          8346                                                                        Glu Lys Leu Lys Lys Lys Val Glu Leu Leu Gl - #u Arg Glu Glu Cys Val                        325      - #           330      - #           335                   - - TAG GTTTGAGAAA CTATTATAGG TAGGTGGTAC CTGTTAGCTT AGTATAAGG - #G               8399                                                                        End                                                                             - - GAGGAGCCGT TTCTTGTTTT AAAGACACGA ACACAAGGCC GTAAGTTTTA TA -              #TGTGAATT   8459                                                                  - - TTGTGCATGT CTGCGAGTCA GCGTCATA ATG TGT GTT TTC CAA - #ATC CTG ATA           8511                                                                                          - #             Met Cys Val - #Phe Gln Ile Leu Ile                             - #                  - #       -15                            - - ATA GTG ACG ACG ATC AAA GTA GCT GGA ACG GC - #C AAC ATA AAT CAT ATA          8559                                                                        Ile Val Thr Thr Ile Lys Val Ala Gly Thr Al - #a Asn Ile Asn His Ile           10                  - #-5                  - #1               5                  - - GAC GTT CCT GCA GGA CAT TCT GCT ACA ACG AC - #G ATC CCG CGA TAT CCA          8607                                                                        Asp Val Pro Ala Gly His Ser Ala Thr Thr Th - #r Ile Pro Arg Tyr Pro                         10     - #             15     - #             20                   - - CCA GTT GTC GAT GGG ACC CTT TAC ACC GAG AC - #G TGG ACA TGG ATT CCC          8655                                                                        Pro Val Val Asp Gly Thr Leu Tyr Thr Glu Th - #r Trp Thr Trp Ile Pro                     25         - #         30         - #         35                       - - AAT CAC TGC AAC GAA ACG GCA ACA GGC TAT GT - #A TGT CTG GAA AGT GCT          8703                                                                        Asn His Cys Asn Glu Thr Ala Thr Gly Tyr Va - #l Cys Leu Glu Ser Ala                 40             - #     45             - #     50                           - - CAC TGT TTT ACC GAT TTG ATA TTA GGA GTA TC - #C TGC ATG AGG TAT GCG          8751                                                                        His Cys Phe Thr Asp Leu Ile Leu Gly Val Se - #r Cys Met Arg Tyr Ala             55                 - # 60                 - # 65                 - # 70        - - GAT GAA ATC GTC TTA CGA ACT GAT AAA TTT AT - #T GTC GAT GCG GGA TCC          8799                                                                        Asp Glu Ile Val Leu Arg Thr Asp Lys Phe Il - #e Val Asp Ala Gly Ser                             75 - #                 80 - #                 85               - - ATT AAA CAA ATA GAA TCG CTA AGT CTG AAT GG - #A GTT CCG AAT ATA TTC          8847                                                                        Ile Lys Gln Ile Glu Ser Leu Ser Leu Asn Gl - #y Val Pro Asn Ile Phe                         90     - #             95     - #            100                   - - CTA TCT ACG AAA GCA AGT AAC AAG TTG GAG AT - #A CTA AAT GCT AGC CTA          8895                                                                        Leu Ser Thr Lys Ala Ser Asn Lys Leu Glu Il - #e Leu Asn Ala Ser Leu                    105          - #       110          - #       115                       - - CAA AAT GCG GGT ATC TAC ATT CGG TAT TCT AG - #A AAT GGG ACG AGG ACT          8943                                                                        Gln Asn Ala Gly Ile Tyr Ile Arg Tyr Ser Ar - #g Asn Gly Thr Arg Thr                120              - #   125              - #   130                           - - GCA AAG CTG GAT GTT GTT GTG GTT GGC GTT TT - #G GGT CAA GCA AGG GAT          8991                                                                        Ala Lys Leu Asp Val Val Val Val Gly Val Le - #u Gly Gln Ala Arg Asp            135                 1 - #40                 1 - #45                 1 -       #50                                                                               - - CGC CTA CCC CAA ATG TCC AGT CCT ATG ATC TC - #A TCC CAC GCC GAT         ATC     9039                                                                     Arg Leu Pro Gln Met Ser Ser Pro Met Ile Se - #r Ser His Ala Asp Ile                           155  - #               160  - #               165               - - AAG TTG TCA TTA AAA AAC TTT AAA GCA TTA GT - #A TAT CAC GTG GGA GAT          9087                                                                        Lys Leu Ser Leu Lys Asn Phe Lys Ala Leu Va - #l Tyr His Val Gly Asp                        170      - #           175      - #           180                   - - ACT ATC AAT GTC TCG ACG GCG GTT ATA CTA GG - #A CCT TCT CCG GAG ATA          9135                                                                        Thr Ile Asn Val Ser Thr Ala Val Ile Leu Gl - #y Pro Ser Pro Glu Ile                    185          - #       190          - #       195                       - - TTC ACA TTG GAA TTT AGG GTG TTG TTC CTC CG - #T TAT AAT CCA ACG TGC          9183                                                                        Phe Thr Leu Glu Phe Arg Val Leu Phe Leu Ar - #g Tyr Asn Pro Thr Cys                200              - #   205              - #   210                           - - AAG TTC GTC ACG ATT TAT GAA CCT TGT ATA TT - #T CAC CCC AAA GAA CCA          9231                                                                        Lys Phe Val Thr Ile Tyr Glu Pro Cys Ile Ph - #e His Pro Lys Glu Pro            215                 2 - #20                 2 - #25                 2 -       #30                                                                               - - GAG TGT ATT ACT ACT GCA GAA CAA TCG GTA TG - #T CAT TTC GCA TCC         AAC     9279                                                                     Glu Cys Ile Thr Thr Ala Glu Gln Ser Val Cy - #s His Phe Ala Ser Asn                           235  - #               240  - #               245               - - ATT GAC ATT CTG CAG ATA GCC GCC GCA CGT TC - #T GAA AAT TGT AGC ACA          9327                                                                        Ile Asp Ile Leu Gln Ile Ala Ala Ala Arg Se - #r Glu Asn Cys Ser Thr                        250      - #           255      - #           260                   - - GGG TAT CGT AGA TGT ATT TAT GAC ACG GCT AT - #C GAT GAA TCT GTG CAG          9375                                                                        Gly Tyr Arg Arg Cys Ile Tyr Asp Thr Ala Il - #e Asp Glu Ser Val Gln                    265          - #       270          - #       275                       - - GCC AGA TTA ACA TTC ATA GAA CCA GGA ATT CC - #T TCC TTT AAA ATG AAA          9423                                                                        Ala Arg Leu Thr Phe Ile Glu Pro Gly Ile Pr - #o Ser Phe Lys Met Lys                280              - #   285              - #   290                           - - GAT GTC CAG GTA GAC GAT GCT GGA TTG TAT GT - #G GTT GTG GCT TTA TAC          9471                                                                        Asp Val Gln Val Asp Asp Ala Gly Leu Tyr Va - #l Val Val Ala Leu Tyr            295                 3 - #00                 3 - #05                 3 -       #10                                                                               - - AAT GGA CGT CCA AGT GCA TGG ACT TAC ATT TA - #T TTG TCA ACG GTG         GAA     9519                                                                     Asn Gly Arg Pro Ser Ala Trp Thr Tyr Ile Ty - #r Leu Ser Thr Val Glu                           315  - #               320  - #               325               - - ACA TAT CTT AAT GTA TAT GAA AAC TAC CAC AA - #G CCG GGA TTT GGG TAT          9567                                                                        Thr Tyr Leu Asn Val Tyr Glu Asn Tyr His Ly - #s Pro Gly Phe Gly Tyr                         330     - #           335      - #           340                   - - AAA TCA TTT CTA CAG AAC AGT AGT ATC GTC GA - #C GAA AAT GAG GCT AGC          9615                                                                        Lys Ser Phe Leu Gln Asn Ser Ser Ile Val As - #p Glu Asn Glu Ala Ser                    345          - #       350          - #       355                       - - GAT TGG TCC AGC TCG TCC ATT AAA CGG AGA AA - #T AAT GGT ACT ATC ATT          9663                                                                        Asp Trp Ser Ser Ser Ser Ile Lys Arg Arg As - #n Asn Gly Thr Ile Ile                360              - #   365              - #   370                           - - TAT GAT ATT TTA CTC ACA TCG CTA TCA ATT GG - #G GCG ATT ATT ATC GTC          9711                                                                        Tyr Asp Ile Leu Leu Thr Ser Leu Ser Ile Gl - #y Ala Ile Ile Ile Val            375                 3 - #80                 3 - #85                 3 -       #90                                                                               - - ATA GTA GGG GGT GTT TGT ATT GCC ATA TTA AT - #T AGG CGT AGG AGA         CGA     9759                                                                     Ile Val Gly Gly Val Cys Ile Ala Ile Leu Il - #e Arg Arg Arg Arg Arg                           395  - #               410  - #               415               - - CGT CGC ACG AGG GGG TTA TTC GAT GAA TAT CC - #C AAA TAT ATG ACG CTA          9807                                                                        Arg Arg Thr Arg Gly Leu Phe Asp Glu Tyr Pr - #o Lys Tyr Met Thr Leu                        420      - #           425      - #           430                   - - CCA GGA AAC GAT CTG GGG GGC ATG AAT GTA CC - #G TAT GAT AAT ACA TGC          9855                                                                        Pro Gly Asn Asp Leu Gly Gly Met Asn Val Pr - #o Tyr Asp Asn Thr Cys                    435          - #       440          - #       445                       - - TCT GGT AAC CAA GTT GAA TAT TAT CAA GAA AA - #G TCG GCT AAA ATG AAA          9903                                                                        Ser Gly Asn Gln Val Glu Tyr Tyr Gln Glu Ly - #s Ser Ala Lys Met Lys                450              - #   455              - #   460                           - - AGA ATG GGT TCG GGT TAT ACC GCT TGG CTA AA - #A AAT GAT ATG CCG AAA          9951                                                                        Arg Met Gly Ser Gly Tyr Thr Ala Trp Leu Ly - #s Asn Asp Met Pro Lys            465                 4 - #70                 4 - #75                 4 -       #80                                                                               - - ATT AGG AAA CGC TTA GAT TTA TAC CAC TGA TA - #TGTACATA TTTAAACTTA           10001                                                                       Ile Arg Lys Arg Leu Asp Leu Tyr His End                                                        485                                                             - - ATGGGATATA GTATATGGAC GTCTATATGA CGAGAGTAAA TAAACTGACA AT -              #GCAAATGA  10061                                                                  - - AGCTGATCTA TATTGTGCTT TATATTGGGA CAAACCACTC GCACAAGCTC AT -             #TCAACACA  10121                                                                  - - TCCACTCTTG CTATTAAATT CCCCATTATA TAACAATACT GACATAACAC TC -             #ATATTAAG  10181                                                                  - - GGGAGAAAAT AAATATGCAT GGCCGATCAT ATTTTATTGA GATCCGAAAA TA -             #TATCATGC  10241                                                                  - - AAATAAGCAT GTTCTAGCAC CACTGCAACA TGTGGTTTAT CGATTTCCGG AA -             #AGAATAGT  10301                                                                  - - TGAACCATTG CCTCCGAGCA GTTGGCGATC CGTTGACCTG CAGGTCGAC  - #                 10350                                                                         - -  - - (2) INFORMATION FOR SEQ ID NO:2:                                      - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH:  10350 b - #ase pairs                                              (B) TYPE:  nucleic a - #cid                                                    (C) STRANDEDNESS:  doub - #le                                                  (D) TOPOLOGY:  linear                                                 - -     (ii) MOLECULE TYPE:                                                             (A) DESCRIPTION:  genom - #ic DNA                                     - -    (iii) HYPOTHETICAL:  Yes                                                - -     (iv) ANTI-SENSE:  Yes                                                  - -     (vi) ORIGINAL SOURCE:                                                           (A) ORGANISM:  MDV, - #GA strain                                      - -    (vii) IMMEDIATE SOURCE:                                                          (A) LIBRARY:  genomic                                                 - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #2:                           - - GTCGACCTGC AGGTCAACGG ATCGCCAACT GCTCGGAGGC AATGGTTCAA CT -              #ATTCTTTC     60                                                                  - - CGGAAATCGA TAAACCACAT GTTGCAGTGG TGCTAGAACA TGCTTATTTG CA -             #TGATATAT    120                                                                  - - TTTCGGATCT CAATAAAATA TGATCGGCCA TGCATATTTA TTTTCTCCCC TT -             #AATATGAG    180                                                                  - - TGTTATGTCA GTATTGTTAT ATAATGGGGA ATTTAATAGC AAGAGTGGAT GT -             #GTTGAATG    240                                                                  - - AGCTTGTGCG AGTGGTTTGT CCCAATATAA AGCACAATAT AGATCAGCTT CA -             #TTTGCATT    300                                                                  - - GTCAGTTTAT TTACTCTCGT CATATAGACG TCCATATACT ATATCCCATT AA -             #GTTTAAAT    360                                                                  - - ATGTACATAT CAGTGGTATA AATCTAAGCG TTTCCTAATT TTCGGCATAT CA -             #TTTTTTAG    420                                                                  - - CCAAGCGGTA TAACCCGAAC CCATTCTTTT CATTTTAGCC GACTTTTCTT GA -             #TAATATTC    480                                                                  - - AACTTGGTTA CCAGAGCATG TATTATCATA CGGTACATTC ATGCCCCCCA GA -             #TCGTTTCC    540                                                                  - - TGGTAGCGTC ATATATTTGG GATATTCATC GAATAACCCC CTCGTGCGAC GT -             #CGTCTCCT    600                                                                  - - ACGCCTAATT AATATGGCAA TACAAACACC CCCTACTATG ACGATAATAA TC -             #GCCCCAAT    660                                                                  - - TGATAGCGAT GTGAGTAAAA TATCATAAAT GATAGTACCA TTATTTCTCC GT -             #TTAATGGA    720                                                                  - - CGAGCTGGAC CAATCGCTAG CCTCATTTTC GTCGACGATA CTACTGTTCT GT -             #AGAAATGA    780                                                                  - - TTTATACCCA AATCCCGGCT TGTGGTAGTT TTCATATACA TTAAGATATG TT -             #TCCACCGT    840                                                                  - - TGACAAATAA ATGTAAGTCC ATGCACTTGG ACGTCCATTG TATAAAGCCA CA -             #ACCACATA    900                                                                  - - CAATCCAGCA TCGTCTACCT GGACATCTTT CATTTTAAAG GAAGGAATTC CT -             #GGTTCTAT    960                                                                  - - GAATGTTAAT CTGGCCTGCA CAGATTCATC GATAGCCGTG TCATAAATAC AT -             #CTACGATA   1020                                                                  - - CCCTGTGCTA CAATTTTCAG AACGTGCGGC GGCTATCTGC AGAATGTCAA TG -             #TTGGATGC   1080                                                                  - - GAAATGACAT ACCGATTGTT CTGCAGTAGT AATACACTCT GGTTCTTTGG GG -             #TGAAATAT   1140                                                                  - - ACAAGGTTCA TAAATCGTGA CGAACTTGCA CGTTGGATTA TAACGGAGGA AC -             #AACACCCT   1200                                                                  - - AAATTCCAAT GTGAATATCT CCGGAGAAGG TCCTAGTATA ACCGCCGTCG AG -             #ACATTGAT   1260                                                                  - - AGTATCTCCC ACGTGATATA CTAATGCTTT AAAGTTTTTT AATGACAACT TG -             #ATATCGGC   1320                                                                  - - GTGGGATGAG ATCATAGGAC TGGACATTTG GGGTAGGCGA TCCCTTGCTT GA -             #CCCAAAAC   1380                                                                  - - GCCAACCACA ACAACATCCA GCTTTGCAGT CCTCGTCCCA TTTCTAGAAT AC -             #CGAATGTA   1440                                                                  - - GATACCCGCA TTTTGTAGGC TAGCATTTAG TATCTCCAAC TTGTTACTTG CT -             #TTCGTAGA   1500                                                                  - - TAGGAATATA TTCGGAACTC CATTCAGACT TAGCGATTCT ATTTGTTTAA TG -             #GATCCCGC   1560                                                                  - - ATCGACAATA AATTTATCAG TTCGTAAGAC GATTTCATCC GCATACCTCA TG -             #CAGGATAC   1620                                                                  - - TCCTAATATC AAATCGGTAA AACAGTGAGC ACTTTCCAGA CATACATAGC CT -             #GTTGCCGT   1680                                                                  - - TTCGTTGCAG TGATTGGGAA TCCATGTCCA CGTCTCGGTG TAAAGGGTCC CA -             #TCGACAAC   1740                                                                  - - TGGTGGATAT CGCGGGATCG TCGTTGTAGC AGAATGTCCT GCAGGAACGT CT -             #ATATGATT   1800                                                                  - - TATGTTGGCC GTTCCAGCTA CTTTGATCGT CGTCACTATT ATCAGGATTT GG -             #AAAACACA   1860                                                                  - - CATTATGACG CTGACTCGCA GACATGCACA AAATTCACAT ATAAAACTTA CG -             #GCCTTGTG   1920                                                                  - - TTCGTGTCTT TAAAACAAGA AACGGCTCCT CCCCTTATAC TAAGCTAACA GG -             #TACCACCT   1980                                                                  - - ACCTATAATA GTTTCTCAAA CCTATACACA TTCTTCTCTT TCCAACAATT CG -             #ACTTTCTT   2040                                                                  - - CTTCAGTTTT TCCATCAACT CCTTTTCAAT AACATCTGAA GGAGTTTCCT TT -             #ACATTATA   2100                                                                  - - ATCATATTGA AATGATTCGT TAACTGCAGA AGTGATGAGT GGGGCCTCAT CA -             #GATCTTGG   2160                                                                  - - TTCACCGATG TATATCCTAC GATGGGGAGA GCGGCACCTT TCACAGACCA AA -             #TAAATTGC   2220                                                                  - - CAATGCTATT ATACATAGTA CAATCATCGT AGAAAAGTAA ATAAGCCTTG GA -             #AGGGTATA   2280                                                                  - - TTTTAAAACG GTATTCCACA TACCAGTCGA ATTCATTGCA TCGACATGGG AA -             #TTGTTATT   2340                                                                  - - AAACAAATTA AAAACCGTAG GTGAATAAAT TGTTCCCGAA TTATCGTAAA AT -             #GGAGTCGT   2400                                                                  - - TACAATATTA ATATCTGTGG AAATGGATTG GGGAGTAATA TTATAAATTG CA -             #TGCAATTC   2460                                                                  - - CGAGTCACTG TCCAGCAAAT TGCCTACATG TCCAATCAGA TAATTTTCAA AG -             #GCCATACG   2520                                                                  - - GTCGACATAG CGAATACATT TATGGGCCTG AAATGAACTA GCAGAGTGAT TA -             #CAGGCCCA   2580                                                                  - - AGATTTGCTA CTCCTTATAA TAACAACCAT TCTAAATATA TCGCTCATAT TT -             #CTTCCAGC   2640                                                                  - - GAGAGATACA CGTATGTAAT AGCTGCCTGT ATCTGATACT CTGGGTTCGA CA -             #ATTCTCAA   2700                                                                  - - CAATGTTCCC TTTTCGGGAA AAGGTTGTAC TCTACCATGA GGTTGAGCAT AT -             #ACCACAGC   2760                                                                  - - GTCTCTACAG CCTCTGAATA CCGTGGCGTC TATAGCAGGA CAATCCATAT AT -             #GATGTCGC   2820                                                                  - - ATGTAGAACG GAATAGCATT TATATTCTTC ATCCCATTTC AAGATTTCCG TC -             #GTTCCTGT   2880                                                                  - - ATAAGAACTG GTCCGAGTCT GGTCGCCCAG GAATAAAAGT TGGCCGCGTA CA -             #TTCACCAT   2940                                                                  - - TTTATCTAAT CCGCGGAACG CAACAAGAGC AGATTGGTCC GTTGATAACG TA -             #ACAGATGT   3000                                                                  - - TCCAGTATAA ACTATAGACC AGATGCCTCG AAAGAGGCGG ATCCAAAATA AT -             #AATTGTAG   3060                                                                  - - TACATACATC GCAATCACAC ACGCCGTCTA TCTGACCAAA GAAGCTATAT AA -             #TGTCATTG   3120                                                                  - - ATCAATGTAG TCAACTTCTT ATGCACTATA GCGACACGCC CATACCAAAC AC -             #GTGTTATA   3180                                                                  - - GGCGGGAATA TGCCCGTCTT GATGGACGAC GTCTATCATA CATCACCGTT TT -             #GCGGTGTT   3240                                                                  - - TGCGAAGGAT CCATATACCA GACCCGATTA CAATGAAACA AAACATGACG CA -             #TAGAACAA   3300                                                                  - - CTAGTGAAAT TATTATTTGC GTTCGGGATT TTTTTTCTGT TGATATTTTA GG -             #TGATTGAC   3360                                                                  - - TGGATGCCTC CTCGACAGAG ATTATCGGTC GTTTAGTTAT GTATGGTGCT TT -             #CTCAAAGT   3420                                                                  - - CCTCGGGCCG ATTAGTGAGT CCAGTGTAAC CATCCACGGA GGTGGTAATG TT -             #ATTAGTAG   3480                                                                  - - TGGCCGATGT CATTTTGACG TCATTATATT TATCGTCGTC AGGTGATTTT AA -             #ATATGAAT   3540                                                                  - - CTCTAAAACT TCTCGGCAAA TTTGAGACTT GTTGCATAGA TGTTTCGACG AC -             #GATTGGTA   3600                                                                  - - GATGTTTACC ACCATTTCGT TCAAGCCACT GCTTCACATT TTCTTCATGG GC -             #TCTCGGGG   3660                                                                  - - TTCCTGTTCG CACCATGTCT AACAGCCGTG TTGTACCATT GACAAAAAAA CT -             #GAACGGTT   3720                                                                  - - TGCATAGTTT GTTATCCTTT ATCCCCCGTC TCGAAAAACT ACATGTTCCT TT -             #AACAGTCA   3780                                                                  - - GTAATATGTC ACTCGAAATG GGTTCTCCAT TAATAATTAT TAAACGCGTA TA -             #TAATCCAC   3840                                                                  - - TTAGCTCACG ACTGGGTGCT GCAATAATCA ATTTCAATTC ATCTCGATCG AT -             #ATAACTCG   3900                                                                  - - TCATTGCATA TCTTCTATCC CACCATCCTA GGGACTTTAA TTTACAAGTT CC -             #AAATGGTT   3960                                                                  - - CATTAGTAGA GCAGTTGGCA TATTCACGTA AATAAATTGG TCTCCCACAT GC -             #TCTGCCCA   4020                                                                  - - AGACAAACCA TGCTACTAGA GCATCATATT TGCGTCGTCC CATCAACAGT AA -             #ACTGAGAA   4080                                                                  - - GCGTATATTT CGGATCGCCA AATGGATTCA AAACAGCAAA ACTACAATTA TC -             #CGTATATA   4140                                                                  - - TTACGTGTTT TGTCTCATAT GAATTGTCAA GTGTATCAAA CAGTGGAGAC GG -             #GATTTTGT   4200                                                                  - - ATTCATTGAG AGTAGCCCGG AGGTTTTCAT TACCTTTCGG ATGTAATGTG GG -             #AATGATCG   4260                                                                  - - GAGAATTGTC TTTCTTAAGT CCCATTGCGG ACATGTCCCC AGTTCCCAAA AG -             #TAAACAGA   4320                                                                  - - TTATAAGAAT CATTCTCGTG GATGAGATAT ATCTAAAAAA AATACTTTCA TA -             #TCTGTATC   4380                                                                  - - TATTCATACC GAAGCTCTAA AAGGTGCCAA TATAACAGTT ATAGGAGACG CT -             #ATATATAT   4440                                                                  - - TTTTATTTCC GTTATGTTCG ACGTTAAGCA GTTGTTTCTT GTAACTTAGT AT -             #ACGTTAGT   4500                                                                  - - CATATCCCGA CGATGAAAAT AAGTATATAA GAAACGATCT GATATATTAT AA -             #TGTTAGAA   4560                                                                  - - AAATGAGAAT GAAATTTTTA TTCCGTTACC AGCGCCAATT GATTCACATT TC -             #AAAGATAC   4620                                                                  - - CTTAAATATC TCGGGATTCT TCCATCGCCT CTTAGAGGAA CGTATATATT TT -             #TCACGACG   4680                                                                  - - TAGACCACTA TTGCCATGGG AGTTCAGATT TTGCCATGAA AAATCACGAC TT -             #CGGTCAGG   4740                                                                  - - CTTACGAACT TTATAAAAAA CACTTTTAGG GTCCTCTGCC TGCATCGAAG GT -             #CCATTTAT   4800                                                                  - - TAATGGACAT TCTTCCGAAT CGTTCATTAC AGACATGCTT GAAGTAACAT TG -             #GATTGTGC   4860                                                                  - - TAAGGAGTTA TGTATGTCTG AACATCTATC ATCTACCTTA CTCTCATCGT TT -             #AGAGTATA   4920                                                                  - - TCTCATGCAA TCCGAAAATG TTCCATAATG CTTTATTTGC GGTCTGTGGG AA -             #TATGGCGT   4980                                                                  - - AGGTCCCGAA GGTGCCATTC GCAAAAAAGG TCTGCGAATC TTCAAAGACT TC -             #GAATGTTG   5040                                                                  - - TCATTATTGC AGGTAACGCG TAGTATATAT TATAAAATGA ATCATTGAAG TT -             #ATTTTTGA   5100                                                                  - - CGGGTGTTTA CATATGAGCG GCAGTTATCG TGTATAATGC GTCAGCGGGT TC -             #TTTAGTAA   5160                                                                  - - AAAGAGGCAA CATTAAAATA TCTTGGGCAG ATGGTCTAAA CTCCTGATCG AA -             #TGTGAGCA   5220                                                                  - - TTTTTGCAAT AGCATATTCA AGATCCATCG TCATACCACT CTTTCGTATA AT -             #CTGAGGGA   5280                                                                  - - TTGCATATGG ATGTCGTAAC TGAATCGCGT ACTGCTTGAA GTGTTTGCAT AA -             #GTTTGTAG   5340                                                                  - - AATTGTTCTG TGGAAATTCC AACGGATGGA CTTGCAGGCA TCTAATTATG GA -             #TCTCAGCT   5400                                                                  - - GAGAACCTGA GCCGTTTACT TGTTTGCCAA AAAAGGTTAT ATTTTTTACT GA -             #CATCTCAA   5460                                                                  - - ACAGAACTAA TCCTGCACTC CATATATCAG TTTTTGTACA GTATGGATCA AG -             #TGCAAGCA   5520                                                                  - - GTTCAGGCGA ATTGGTTTCC AGAGTTCCAC TCCATCCATA ACATTTGGGT TT -             #ATCTGTAT   5580                                                                  - - GTTCATCTAA TTTACATGCT GCCCCAAAGT CCCCCAATAC TACATTTTCA GG -             #TTTATCCA   5640                                                                  - - AAAATATATT TTCAGTTTTT ACATCACGAT GTATTATACC CTTTTCGTGG AT -             #ATATGCCA   5700                                                                  - - ATGCTCCAAG CAAACCCCGT TCTATCGTAA TTATTTGATT TAGTGGCAAT GG -             #TCCCATGA   5760                                                                  - - TATCTATGTA CGTAAACAAG TCGCATTTGT ATTTAGGCAT TACCATACAA AC -             #TGTCGATT   5820                                                                  - - TCCATCTATA AGCATGAACT AATCTAATTA TGGAGCGGTG AGACATTTTT TT -             #TAATATAT   5880                                                                  - - CAATTTCACT CCCAAGGGTT TTGCCACCAG TCACAGCTTT CACAATGACT TT -             #TCTCTTGG   5940                                                                  - - TATTATCCCC ACGCTTTGTA CAAACATAGA TATACCCTTC AGATCCGGGC GG -             #TAACGATG   6000                                                                  - - AAACAATGTT ATACTGCATT CGCACAGCTG AAACTGCATC AATGTCCGTC AC -             #CGTTTCGG   6060                                                                  - - GGGATTCATT TCCATCGTTC CCAAAAGGTG ACAAATCTTC AGATTGGGAC TC -             #GGGAGAGC   6120                                                                  - - TCTCAGTCTT CACATCGTCC ACATCCCCCG TCACTTCCGC GTTATCGGTA CT -             #GTCGGGAA   6180                                                                  - - AAGTATCAAA CAACGTCGTA TCCGTACCAT TGATGCTGTT ATGTATAATT CC -             #GTAGGTAG   6240                                                                  - - TATTAGTTTT AGAGTCGTGT ACTTTCGACG AAGAAATGCC ACATTCCATC GT -             #TTCTGCCT   6300                                                                  - - CCGGAGTCGA AGACATCCAG TCTATTACCT AGTTTTAACC CTGTTTCATA TT -             #CTACCAGA   6360                                                                  - - GTATAAGATT TGGAGATCAG ACCGGCCCAG TTATTAACAA TAAAAAAGAT TA -             #TTGGTGGA   6420                                                                  - - GGTGAAG  ATG GGT GTG TCC ATG ATA ACT ATA G - #TC ACA CTT CTA GAT        GAA    6469                                                                               Met Gly Val Ser Met I - #le Thr Ile Val Thr Leu Leu Asp Glu                   1         - #      5            - #       10                           - - TGC GAT CGA TTG CCA GGA AGA TCT AGA GAT GC - #T GCA TCT ACT TTA TGG          6517                                                                        Cys Asp Arg Leu Pro Gly Arg Ser Arg Asp Al - #a Ala Ser Thr Leu Trp             15                 - # 20                 - # 25                 - # 30        - - ATA TTC CTT ATA AAG CAA TGT ATG GAA CAA AT - #A CAG GAT GAT GTG GGT          6565                                                                        Ile Phe Leu Ile Lys Gln Cys Met Glu Gln Il - #e Gln Asp Asp Val Gly                             35 - #                 40 - #                 45               - - GTG CCC ATA ATC GCC AGA GCT GCA GAC CTA TT - #C CGT TTT GCC AAA CCC          6613                                                                        Val Pro Ile Ile Ala Arg Ala Ala Asp Leu Ph - #e Arg Phe Ala Lys Pro                         50     - #             55     - #             60                   - - ATG TTA ATT CTT CCT CGG CAA CAT CGA CCG AT - #A GTA AGG ACA AAG CCA          6661                                                                        Met Leu Ile Leu Pro Arg Gln His Arg Pro Il - #e Val Arg Thr Lys Pro                     65         - #         70         - #         75                       - - CCA GAT GGA ACT GGA GTT CGT GGT ACC GGA TT - #G GCC GGA ACT AGG GAT          6709                                                                        Pro Asp Gly Thr Gly Val Arg Gly Thr Gly Le - #u Ala Gly Thr Arg Asp                 80             - #     85             - #     90                           - - TCG TTT ATA GTG CGG CTA TTT GAA GAT GTT GC - #A GGA TGT TCC ACA GAA          6757                                                                        Ser Phe Ile Val Arg Leu Phe Glu Asp Val Al - #a Gly Cys Ser Thr Glu             95                 - #100                 - #105                 - #110        - - TGG CAG GAT GTT CTA TCT GGA TAT TTG ATG TT - #G GAA TCT GAA GTT TCT          6805                                                                        Trp Gln Asp Val Leu Ser Gly Tyr Leu Met Le - #u Glu Ser Glu Val Ser                            115  - #               120  - #               125               - - GGT AAT GCT CCA CAT AGC TTG TGG ATA GTT GG - #G GCG GCA GAT ATA TGT          6853                                                                        Gly Asn Ala Pro His Ser Leu Trp Ile Val Gl - #y Ala Ala Asp Ile Cys                        130      - #           135      - #           140                   - - GCC ATT GCG CTC GAA TGT ATT CCT TTG CCA AA - #A AGG TTA CTT GCA ATC          6901                                                                        Ala Ile Ala Leu Glu Cys Ile Pro Leu Pro Ly - #s Arg Leu Leu Ala Ile                    145          - #       150          - #       155                       - - AAA GTG TCT GGG ACC TGG TCC GGT ATG CCG TG - #G GCC ATT CCC GAC AAT          6949                                                                        Lys Val Ser Gly Thr Trp Ser Gly Met Pro Tr - #p Ala Ile Pro Asp Asn                160              - #   165              - #   170                           - - ATT CAA ACT CTC TTG ACA TCT ACA TGG GAA CC - #G AAG TTC GAC ACC CCA          6997                                                                        Ile Gln Thr Leu Leu Thr Ser Thr Trp Glu Pr - #o Lys Phe Asp Thr Pro            175                 1 - #80                 1 - #85                 1 -       #90                                                                               - - GAA GAT AGA GCG CAT TTT TGC GAC AGT GAT AT - #G GTA TGT GTA TAC         AAA     7045                                                                     Glu Asp Arg Ala His Phe Cys Asp Ser Asp Me - #t Val Cys Val Tyr Lys                           195  - #               200  - #               205               - - ATC CTC GGG TCC CCA CCC AAT CCT CTA AAA CC - #T CCG GAA ATC GAA CCA          7093                                                                        Ile Leu Gly Ser Pro Pro Asn Pro Leu Lys Pr - #o Pro Glu Ile Glu Pro                        210      - #           215      - #           220                   - - CCT CAA ATG AGT AGT ACA CCC GGC AGA TTA TT - #C TGT TGT GGA AAA TGT          7141                                                                        Pro Gln Met Ser Ser Thr Pro Gly Arg Leu Ph - #e Cys Cys Gly Lys Cys                    225          - #       230          - #       235                       - - TGC AAG AAA GAA GAT AGA GAT GCG ATT GCA AT - #T CCG GTT CGT TAC ACT          7189                                                                        Cys Lys Lys Glu Asp Arg Asp Ala Ile Ala Il - #e Pro Val Arg Tyr Thr                240              - #   245              - #   250                           - - GCG ACA GGA AAG TCA CGA ATA CAG AAA AAA TG - #T AGA GCC GGT AGT CAT          7237                                                                        Ala Thr Gly Lys Ser Arg Ile Gln Lys Lys Cy - #s Arg Ala Gly Ser His            255                 2 - #60                 2 - #65                 2 -       #70                                                                               - - TAG  CTGTTATTCG ACAGACCTAC TTGCTACCAA TTAGATATAA TTACA - #TGATG              7290                                                                        - - GGGCGTATAC ACATTACGAT TAGGTGCATC GCTACAACCG TCGCTATAGT GT -              #CACGTATA   7350                                                                  - - ATTTGTATAT TAGTGCAATA ACAAACCCTT CTAGATCACT TATGTATCCA GG -             #CTATCTTC   7410                                                                  - - CATATACTTC TAACATCAGG AGAGATTCAA CAATCGAGCG CATTTGAAAG AC - #AACG       ATG   7469                                                                                         - #                  - #                  - #              Met                                                                                                - #                  - #                  - #                - - AGC AGA GTC AAT GCT ACA ATG TTC GAT GAT AT - #G GAT ATA CCA AGA GGA          7517                                                                        Ser Arg Val Asn Ala Thr Met Phe Asp Asp Me - #t Asp Ile Pro Arg Gly                         5     - #              10    - #              15                   - - CGA TTT GGT AAG CCA CCG AGA AAG ATT ACT AA - #T GTA AAT TTT TGG CAT          7565                                                                        Arg Phe Gly Lys Pro Pro Arg Lys Ile Thr As - #n Val Asn Phe Trp His                     20         - #         25         - #         30                       - - GTG GTT GTT GAT GAA TTC ACA GAA GGA ATC GT - #T CAA TGT ATG GAA GCC          7613                                                                        Val Val Val Asp Glu Phe Thr Glu Gly Ile Va - #l Gln Cys Met Glu Ala                 35             - #     40             - #     45                           - - CGA GAG AGA TTA GGC CTT TTA TGT ACC ATA TC - #T ACT AAC GAG GGA TCT          7661                                                                        Arg Glu Arg Leu Gly Leu Leu Cys Thr Ile Se - #r Thr Asn Glu Gly Ser             50                 - # 55                 - # 60                 - # 65        - - ATT ACA TCG TTT GAT ATA CAC AAG GAT ATG TG - #G TGT CAA ATG GTT ATC          7709                                                                        Ile Thr Ser Phe Asp Ile His Lys Asp Met Tr - #p Cys Gln Met Val Ile                             70 - #                 75 - #                 80               - - TGG TCT GCC TAT AGA TTT TTT GCC ATG ATG GA - #C AAA ATG TTT TCG ATT          7757                                                                        Trp Ser Ala Tyr Arg Phe Phe Ala Met Met As - #p Lys Met Phe Ser Ile                         85     - #             90     - #             95                   - - GAA ACT ATC ACA AAT TTT ACA GAA ACT GAT CT - #T ACC GAA ACT GGT CAG          7805                                                                        Glu Thr Ile Thr Asn Phe Thr Glu Thr Asp Le - #u Thr Glu Thr Gly Gln                    100          - #       105          - #       110                       - - TGG AGA ATA TTC TAT AGA ACT TGG GAT GTG AG - #A GAT GCA TTG AAG ATG          7853                                                                        Trp Arg Ile Phe Tyr Arg Thr Trp Asp Val Ar - #g Asp Ala Leu Lys Met                115              - #   120              - #   125                           - - AAA CAG GTG GGA CCA TTT TTG CCC GCA TTG TT - #T TCA TTT CAT CTG GAA          7901                                                                        Lys Gln Val Gly Pro Phe Leu Pro Ala Leu Ph - #e Ser Phe His Leu Glu            130                 1 - #35                 1 - #40                 1 -       #45                                                                               - - AAC TGG ACC ACA ATG CTT TCC ATA GGA ATC AA - #C AAG GGT TAT GAT         CGA     7949                                                                     Asn Trp Thr Thr Met Leu Ser Ile Gly Ile As - #n Lys Gly Tyr Asp Arg                           150  - #               155  - #               160               - - CAC AAT ACA CGA AAT ATG TTC ATG ACA ATA CA - #G TCT GCA AGA AAT GTC          7997                                                                        His Asn Thr Arg Asn Met Phe Met Thr Ile Gl - #n Ser Ala Arg Asn Val                        165      - #           170      - #           175                   - - CTT AGC GGG GCA ATA GAG GTA GCT CGA TAT GC - #C GTG GTT CTT GCT CTA          8045                                                                        Leu Ser Gly Ala Ile Glu Val Ala Arg Tyr Al - #a Val Val Leu Ala Leu                    180          - #       185          - #       190                       - - CCT GTG TGC GAG TAT AGA ACA CCC TTA GGC CT - #G CCG GAT GAT AGC ATA          8093                                                                        Pro Val Cys Glu Tyr Arg Thr Pro Leu Gly Le - #u Pro Asp Asp Ser Ile                195              - #   200              - #   205                           - - GGA AAT GCC ATC AAG ACA TGC TGC ACG CAA AT - #G CAA GCG AAT CGA TTG          8141                                                                        Gly Asn Ala Ile Lys Thr Cys Cys Thr Gln Me - #t Gln Ala Asn Arg Leu            210                 2 - #15                 2 - #20                 2 -       #25                                                                               - - ACA GAA ACT GGA ATA TCC AAG GAC AGT GGA CA - #T AAA ATA AAT GAT         TCT     8189                                                                     Thr Glu Thr Gly Ile Ser Lys Asp Ser Gly Hi - #s Lys Ile Asn Asp Ser                           230  - #               235  - #               240               - - TCT GAA GAG GAG TTG TAT TAT AGA ACC ATA CA - #T GAT CTT ATC AAA CCT          8237                                                                        Ser Glu Glu Glu Leu Tyr Tyr Arg Thr Ile Hi - #s Asp Leu Ile Lys Pro                        245      - #           250      - #           255                   - - AAC CGG GAA CAT TGC ATA TCA TGC AAT ATT GA - #G AAT AGC ATG GAT ATA          8285                                                                        Asn Arg Glu His Cys Ile Ser Cys Asn Ile Gl - #u Asn Ser Met Asp Ile                    260          - #       265          - #       270                       - - GAT CCC ACT ATT CAC CAT CGA TCT TCT AAT GT - #C ATA ACT TTA CAA GGT          8333                                                                        Asp Pro Thr Ile His His Arg Ser Ser Asn Va - #l Ile Thr Leu Gln Gly                275              - #   280              - #   285                           - - ACA TCA ACA TAT CCA TTT GGA CGC AGG CCG AT - #G AGT CGA ATG GAT GTT          8381                                                                        Thr Ser Thr Tyr Pro Phe Gly Arg Arg Pro Me - #t Ser Arg Met Asp Val            290                 2 - #95                 3 - #00                 3 -       #05                                                                               - - GGA GGT CTT ATG TAC CAG CAC CCC TAC ATT TG - #C CGC AAT CTC CAT         TTA     8429                                                                     Gly Gly Leu Met Tyr Gln His Pro Tyr Ile Cy - #s Arg Asn Leu His Leu                           310  - #               315  - #               320               - - CGT CCG CCT CGA TCC AGA CTA ATG AAT AGT AA - #A ATC CTA CAG ACA TTT          8477                                                                        Arg Pro Pro Arg Ser Arg Leu Met Asn Ser Ly - #s Ile Leu Gln Thr Phe                        325      - #           330      - #           335                   - - AGA CAA AGT TTC AAT CGA AGT AAT CCT CAT GC - #A TAC CCC ATA TAA              8522                                                                        Arg Gln Ser Phe Asn Arg Ser Asn Pro His Al - #a Tyr Pro Ile                    340                 3 - #45                 3 - #50                             - - TACATACAAT CATGACAACA CTGTAATGCC TTATTGAAAA TAAAATTTTA TT -              #ATTTAAAC   8582                                                                  - - AACGTTAGTA GCAGTTTTTC CTAAAATCCT ATTAATAATT GTGCGATTAG TT -             #ATAAGTAG   8642                                                                  - - GATTCCCCGT CTCCTGTTGG CGATTCCCGA AGATTTGTCA GATAATGTGC CA -             #ATTCAGCA   8702                                                                  - - TCATCACCGA TTGCTGCATT CCCCTTAGTA GCGACGGCAC GACATAAAGG TT -             #TCCAATAA   8762                                                                  - - GACTCTATTT CGGGGAGTGG ACTTATTCCA CAGCCCGTTG CCGAACCTAC TA -             #TGTCCATA   8822                                                                  - - AGACGGACAT TCTTCTCATA TAAGCGCGAA ACAGTACAGT ATCCAGCATG TC -             #CAAGACAA   8882                                                                  - - CACCAATACA TCATGATAGT AAACCGAGTG TCCATTTCTT CGTGTGTAAG AG -             #GAGCACGT   8942                                                                  - - TCAATACACC GTAAAGCCCG GCCTACAATT TTTCTCGTCG GGTCTGTCGG GT -             #GGAATGGC   9002                                                                  - - GAAGCAGAAA TATCATATTC GTTAAGCGTG ACAGTCATTC TGTCGAATAT CT -             #CACCCCAC   9062                                                                  - - AAACGAGACG ATGGTGGTTT TCCAGCTTTC ATAGCAGCCT GGGAGATCGT AG -             #CGGCGGTT   9122                                                                  - - AATATGGTCC TGGCTAGACT GCGTACAGAT TTAGGCAATA GCGCAACATG TT -             #CCCCGCCG   9182                                                                  - - GCAGAAAGTA TATCATAACT CTGTTCTTTT GGAGAATCTA CCCGGAGTTG CA -             #CACTCCTG   9242                                                                  - - CTAGATTTGC GCCGTAGAGA CCACATGGCC ATACCTCTCC AATATGTTTT AA -             #TCTTACAC   9302                                                                  - - GGCGCTCGTC TCCAGTATTC AAACACGTTC TCCTCTCATT AGGCTCAACG CC -             #ACATTAAA   9362                                                                  - - TATCTTCATA TACAACAAAA AGGCAACACG TTATTTGACA CGCCCCTTCA TG -             #GATGGGGG   9422                                                                  - - GGGTCAGCGT TTGTTGCAAC AGATCATGAC AAATAAATCC AAAATCTATT AT -             #TTTATCTC   9482                                                                  - - ATTAGATAGA TCAAAGAATG TCGGCTCTAT GTCTAACAAT TAAAATTATA TA -             #ATAAGAGC   9542                                                                  - - TTTCTCTTCA AGTCTGGATA GTTAATGCAA TTTACTGTCT ACCGACAAAT CG -             #TTCATTCC   9602                                                                  - - TTTTACATCG CAGTCTGAAG AAATAGTTCC CGAGGACGCA GCGATTGGGT GA -             #AAAATGCT   9662                                                                  - - ATCGGAGGCA TATATATCGG ATATAGGATG GGCGCTTCGA CTATCAGCAT CC -             #CTCAGAGT   9722                                                                  - - CCTGCGCAGA TGTAGACTTT GGCGTGGGGT CAAATTCATG ATAGTTTCCC AT -             #TCGGCTTG   9782                                                                  - - TTTTAGTCGA TATCCCATTC GACCAATCAT ATGAATATCG AATAGTGCTC TC -             #CGAAGAGC   9842                                                                  - - ATCGTGGAAC GGACCGCTAT TTAGTCGACA TCGAATAAAA CATCGAAATA GT -             #TTGTTTGT   9902                                                                  - - ATCCGCACAT AACCGAGCGA CATCGGGTTT CCATGGTAGA GGACAAAATT TG -             #CCCACATT   9962                                                                  - - ATTAAGTTCA AAGTCTTGAT CGGACGAGTC ACTGCCATAT TCCGGATGTG AA -             #TGTGGCAG  10022                                                                  - - TTGATAATCT TCGTCGTCGC TCTCATTATC TGACGATGAT AATCGTGTAT CG -             #GGTCTGGC  10082                                                                  - - TCGATCTCGA TCACGACTCA TGTTGCCTCC GATGGAGCCG AAAGCAGGTT TT -             #CTGCTCAA  10142                                                                  - - GTGTAATTTG GAGACTTTGG CCTGTATTAT ATAGCTACCA GCTTTTATCT TC -             #TGCTAGGA  10202                                                                  - - ACAATAATTG CTAGAATTTA CATCACGTGA TATCCGGTCA AAAATTACTT GG -             #TCTTTAAC  10262                                                                  - - CCAGCCCCTA ATGTACTACT TGCTCTATAT ATTCTCCACA ATGGTAAACC TC -             #CCTCCCTA  10322                                                                  - - AAGATTTCAC TCCAATTTCA AGGAATTC         - #                  - #               10350                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:3:                                      - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH:  497 ami - #no acids                                               (B) TYPE:  amino aci - #ds                                                     (C) STRANDEDNESS:  sing - #le                                                  (D) TOPOLOGY:  linear                                                 - -     (ii) MOLECULE TYPE:                                                             (A) DESCRIPTION:  polyp - #eptide                                     - -     (vi) ORIGINAL SOURCE:                                                           (A) ORGANISM:  MDV, - #GA strain                                      - -    (vii) IMMEDIATE SOURCE:                                                          (A) LIBRARY:  genomic                                                 - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - #3:                           - - Met Cys Val Phe Gln Ile Leu Ile Ile Val Th - #r Thr Ile Lys Val Ala        1              5   - #                 10 - #                 15               - - Gly Thr Ala Asn Ile Asn His Ile Asp Val Pr - #o Ala Gly His Ser Ala                    20     - #             25     - #             30                   - - Thr Thr Thr Ile Pro Arg Tyr Pro Pro Val Va - #l Asp Gly Thr Leu Tyr                35         - #         40         - #         45                       - - Thr Glu Thr Trp Thr Trp Ile Pro Asn His Cy - #s Asn Glu Thr Ala Thr            50             - #     55             - #     60                           - - Gly Tyr Val Cys Leu Glu Ser Ala His Cys Ph - #e Thr Asp Leu Ile Leu        65                 - # 70                 - # 75                 - # 80        - - Gly Val Ser Cys Met Arg Tyr Ala Asp Glu Il - #e Val Leu Arg Thr Asp                        85 - #                 90 - #                 95               - - Lys Phe Ile Val Asp Ala Gly Ser Ile Lys Gl - #n Ile Glu Ser Leu Ser                   100      - #           105      - #           110                   - - Leu Asn Gly Val Pro Asn Ile Phe Leu Ser Th - #r Lys Ala Ser Asn Lys               115          - #       120          - #       125                       - - Leu Glu Ile Leu Asn Ala Ser Leu Gln Asn Al - #a Gly Ile Tyr Ile Arg           130              - #   135              - #   140                           - - Tyr Ser Arg Asn Gly Thr Arg Thr Ala Lys Le - #u Asp Val Val Val Val       145                 1 - #50                 1 - #55                 1 -       #60                                                                               - - Gly Val Leu Gly Gln Ala Arg Asp Arg Leu Pr - #o Gln Met Ser Ser         Pro                                                                                              165  - #               170  - #               175              - - Met Ile Ser Ser His Ala Asp Ile Lys Leu Se - #r Leu Lys Asn Phe Lys                   180      - #           185      - #           190                   - - Ala Leu Val Tyr His Val Gly Asp Thr Ile As - #n Val Ser Thr Ala Val               195          - #       200          - #       205                       - - Ile Leu Gly Pro Ser Pro Glu Ile Phe Thr Le - #u Glu Phe Arg Val Leu           210              - #   215              - #   220                           - - Phe Leu Arg Tyr Asn Pro Thr Cys Lys Phe Va - #l Thr Ile Tyr Glu Pro       225                 2 - #30                 2 - #35                 2 -       #40                                                                               - - Cys Ile Phe His Pro Lys Glu Pro Glu Cys Il - #e Thr Thr Ala Glu         Gln                                                                                               245 - #                250 - #               255              - - Ser Val Cys His Phe Ala Ser Asn Ile Asp Il - #e Leu Gln Ile Ala Ala                   260      - #           265      - #           270                   - - Ala Arg Ser Glu Asn Cys Ser Thr Gly Tyr Ar - #g Arg Cys Ile Tyr Asp               275          - #       280          - #       285                       - - Thr Ala Ile Asp Glu Ser Val Gln Ala Arg Le - #u Thr Phe Ile Glu Pro           290              - #   295              - #   300                           - - Gly Ile Pro Ser Phe Lys Met Lys Asp Val Gl - #n Val Asp Asp Ala Gly       305                 3 - #10                 3 - #15                 3 -       #20                                                                               - - Leu Tyr Val Val Val Ala Leu Tyr Asn Gly Ar - #g Pro Ser Ala Trp         Thr                                                                                              325  - #               330  - #               335              - - Tyr Ile Tyr Leu Ser Thr Val Glu Thr Tyr Le - #u Asn Val Tyr Glu Asn                   340      - #           345      - #           350                   - - Tyr His Lys Pro Gly Phe Gly Tyr Lys Ser Ph - #e Leu Gln Asn Ser Ser               355          - #       360          - #       365                       - - Ile Val Asp Glu Asn Glu Ala Ser Asp Trp Se - #r Ser Ser Ser Ile Lys           370              - #   375              - #   380                           - - Arg Arg Asn Asn Gly Thr Ile Ile Tyr Asp Il - #e Leu Leu Thr Ser Leu       385                 3 - #90                 3 - #95                 4 -       #00                                                                               - - Ser Ile Gly Ala Ile Ile Ile Val Ile Val Gl - #y Gly Val Cys Ile         Ala                                                                                              405  - #               410  - #               415              - - Ile Leu Ile Arg Arg Arg Arg Arg Arg Arg Th - #r Arg Gly Leu Phe Asp                   420      - #           425      - #           430                   - - Glu Tyr Pro Lys Tyr Met Thr Leu Pro Gly As - #n Asp Leu Gly Gly Met               435          - #       440          - #       445                       - - Asn Val Pro Tyr Asp Asn Thr Cys Ser Gly As - #n Gln Val Glu Tyr Tyr           450              - #   455              - #   460                           - - Gln Glu Lys Ser Ala Lys Met Lys Arg Met Gl - #y Ser Gly Tyr Thr Ala       465                 4 - #70                 4 - #75                 4 -       #80                                                                               - - Trp Leu Lys Asn Asp Met Pro Lys Ile Arg Ly - #s Arg Leu Asp Leu         Tyr                                                                                              485  - #               490  - #               495              - - His                                                                        - -  - - (2) INFORMATION FOR SEQ ID NO:4:                                      - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH:  96 amin - #o acids                                                (B) TYPE:  amino aci - #d                                                      (C) STRANDEDNESS:  sing - #le                                                  (D) TOPOLOGY:  linear                                                 - -     (ii) MOLECULE TYPE:  peptide                                           - -    (iii) HYPOTHETICAL:   yes                                               - -      (v) FRAGMENT TYPE:  internal fragment                                 - -     (vi) ORIGINAL SOURCE:                                                           (A) ORGANISM:  MDV                                                             (B) STRAIN:  GA                                                       - -     (ix) FEATURE:                                                                   (A) NAME/KEY:  peptide - #of MDV gene US1 polypeptide                          (B) LOCATION:  32 TO - # 127                                                   (D) OTHER INFORMATION: - # peptide homologous to the US1 gene                       polypeptide - #of herpes simplex virus type 1                    - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: - # 4:                           - - His Pro Glu Tyr Gly Ser Asp Ser Ser Asp Gl - #n Asp Phe Glu Leu Asn                        5 - #                  - #10                  - #15            - - Asn Val Gly Lys Phe Cys Pro Leu Pro Trp Ly - #s Pro Asp Val Ala Arg                    20     - #             25     - #             30                   - - Leu Cys Ala Asp Thr Asn Lys Leu Phe Arg Cy - #s Phe Ile Arg Cys Arg                35         - #         40         - #         45                       - - Leu Asn Ser Gly Pro Phe His Asp Ala Leu Ar - #g Arg Ala Leu Phe Asp            50             - #     55             - #     60                           - - Ile His Met Ile Gly Arg Met Gly Tyr Arg Le - #u Lys Gln Ala Glu Trp        65                 - # 70                 - # 75                 - # 80        - - Glu Thr Ile Met Asn Leu Thr Pro Arg Gln Se - #r Leu His Leu Arg Arg                        85 - #                 90 - #                 95               - -  - - (2) INFORMATION FOR SEQ ID NO:5:                                      - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH:  99 amin - #o acids                                                (B) TYPE:  amino aci - #d                                                      (C) STRANDEDNESS:  sing - #le                                                  (D) TOPOLOGY:  linear                                                 - -     (ii) MOLECULE TYPE:  peptide                                           - -      (v) FRAGMENT TYPE:  internal fragment                                 - -     (vi) ORIGINAL SOURCE:                                                           (A) ORGANISM:  herpes - #simplex virus type 1 (HSV1)                  - -     (ix) FEATURE:                                                                   (A) NAME/KEY:  peptide - #of HSV1 gene US1 polypeptide                         (B) LOCATION:  159 T - #O 257                                                  (D) OTHER INFORMATION: - # peptide homologous to the US1 gene                       polypeptide - #of MDV                                            - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: - # 5:                           - - Arg Ala Pro Thr Pro Ser Ala Pro Ser Pro As - #n Ala Met Leu Arg Arg                        5 - #                  - #10                  - #15            - - Ser Val Arg Gln Ala Gln Arg Arg Ser Ser Al - #a Arg Trp Thr Pro Asp                    20     - #             25     - #             30                   - - Leu Gly Tyr Met Arg Gln Cys Ile Asn Gln Le - #u Phe Arg Val Leu Arg                35         - #         40         - #         45                       - - Val Ala Arg Asp Pro His Gly Ser Ala Asn Ar - #g Leu Arg His Leu Ile            50             - #     55             - #     60                           - - Arg Asp Cys Tyr Leu Met Gly Tyr Cys Arg Al - #a Arg Leu Ala Pro Arg        65                 - # 70                 - # 75                 - # 80        - - Thr Trp Cys Arg Leu Leu Gln Val Ser Gly Gl - #y Thr Trp Gly Met His                        85 - #                 90 - #                 95               - - Leu Arg Asn                                                                - -  - - (2) INFORMATION FOR SEQ ID NO:6:                                      - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH:  98 amin - #o acids                                                (B) TYPE:  amino aci - #d                                                      (C) STRANDEDNESS:  sing - #le                                                  (D) TOPOLOGY:  linear                                                 - -     (ii) MOLECULE TYPE:  peptide                                           - -      (v) FRAGMENT TYPE:  internal fragment                                 - -     (vi) ORIGINAL SOURCE:                                                           (A) ORGANISM:  varicell - #a-zoster virus (VZV)                       - -     (ix) FEATURE:                                                                   (A) NAME/KEY:  peptide - #of VZV gene 63/70 polypeptide                        (B) LOCATION:  26 TO - # 123                                                   (D) OTHER INFORMATION: - #peptide homologous to the US1  gene                       polypeptide - #of herpes simplex virus type 1 OR MDV US1                       gene poly - #peptide                                             - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: - # 6:                           - - Lys Met Glu Tyr Gly Ser Ala Pro Gly Pro Le - #u Asn Gly Arg Asp Thr                        5 - #                  - #10                  - #15            - - Ser Arg Gly Pro Gly Ala Phe Cys Thr Pro Gl - #y Trp Glu Ile His Pro                    20     - #             25     - #             30                   - - Ala Arg Leu Val Glu Asp Ile Asn Arg Val Ph - #e Leu Cys Ile Ala Gln                35         - #         40         - #         45                       - - Ser Ser Gly Arg Val Thr Arg Asp Ser Arg Ar - #g Leu Arg Arg Ile Cys            50             - #     55             - #     60                           - - Leu Asp Phe Tyr Leu Met Gly Arg Thr Arg Gl - #n Arg Pro Thr Leu Ala        65                 - # 70                 - # 75                 - # 80        - - Cys Trp Glu Glu Leu Leu Gln Leu Gln Pro Th - #r Gln Thr Gln Cys Leu                        85 - #                 90 - #                 95               - - Arg Ala                                                                    - -  - - (2) INFORMATION FOR SEQ ID NO:7:                                      - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH:  99 amin - #o acids                                                (B) TYPE:  amino aci - #d                                                      (C) STRANDEDNESS:  sing - #le                                                  (D) TOPOLOGY:  linear                                                 - -     (ii) MOLECULE TYPE:  peptide                                           - -      (v) FRAGMENT TYPE:  internal fragment                                 - -     (vi) ORIGINAL SOURCE:                                                           (A) ORGANISM:  pseudora - #bies virus (PRV)                           - -     (ix) FEATURE:                                                                   (A) NAME/KEY:  peptide - #of PRV US1 polypeptide                               (B) LOCATION: 55 TO - #153                                                     (D) OTHER INFORMATION: - # peptide homologous to the  US1 gene                      polypeptide - #of herpes simplex virus type 1 OR MDV US1                       gene poly - #peptide                                             - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: - # 7:                           - - His Pro Glu Tyr Gly Pro Pro Pro Asp Pro Gl - #u Glu Val Arg Val His                        5 - #                  - #10                  - #15            - - Gly Ala Arg Gly Pro Gly Ala Phe Cys Ala Al - #a Pro Trp Arg Pro Asp                    20     - #             25     - #             30                   - - Val Met Arg Leu Ala Gly Asp Val His Arg Le - #u Phe Arg Gly Leu Ala                35         - #         40         - #         45                       - - Val Ser Ser Ala His Tyr Thr Gly Asp Ser Ar - #g Val Leu Arg Arg Ala            50             - #     55             - #     60                           - - Leu Phe Asp Phe Tyr Ala His Gly Thr Thr Ar - #g Gln Arg Pro Ser Ala        65                 - # 70                 - # 75                 - # 80        - - Pro Cys Trp Gln Ala Leu Leu Gln Leu Ser Pr - #o Glu Gln Ser Ala Pro                        85 - #                 90 - #                 95               - - Leu Arg Ser                                                                - -  - - (2) INFORMATION FOR SEQ ID NO:8:                                      - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH:  99 amin - #o acids                                                (B) TYPE:  amino aci - #d                                                      (C) STRANDEDNESS:  sing - #le                                                  (D) TOPOLOGY:  linear                                                 - -     (ii) MOLECULE TYPE:  peptide                                           - -      (v) FRAGMENT TYPE:  internal fragment                                 - -     (vi) ORIGINAL SOURCE:                                                           (A) ORGANISM:  equine - #herpesvirus type 4 (EHV4)                    - -     (ix) FEATURE:                                                                   (A) NAME/KEY:  peptide - #of EHV4 gene 65 polypeptide                          (B) LOCATION:  51 -1 - #49                                                     (D) OTHER INFORMATION: - # peptide homologous to the US1 gene                       polypeptide - #of herpes simplex virus type 1 OR MDV US1                       gene poly - #peptide                                             - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: - # 8:                           - - His Pro Glu Tyr Gly Leu Pro Leu Ser Pro Ar - #g Ser Leu Arg Pro Tyr                        5 - #                  - #10                  - #15            - - Leu Ser Arg Gly Pro Gly Ala Phe Cys Ala Pr - #o Pro Trp Arg Pro Asp                    20     - #             25     - #             30                   - - Val Asn Arg Leu Ala Gly Asp Val Asn Arg Le - #u Phe Arg Gly Ile Ser                35         - #         40         - #         45                       - - Thr Ser Ser Ile His Val Thr Glu Asp Ser Ar - #g Val Leu Arg Arg Val            50             - #     55             - #     60                           - - Leu Leu Asp Phe Tyr Ala Met Gly Tyr Thr Hi - #s Ala Arg Pro Thr Leu        65                 - # 70                 - # 75                 - # 80        - - Glu Cys Trp Gln Ala Leu Leu Gln Leu Met Pr - #o Glu Gln Ser Leu Pro                        85 - #                 90 - #                 95               - - Leu Arg Ala                                                                - -  - - (2) INFORMATION FOR SEQ ID NO:9:                                      - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH:  93 amin - #o acids                                                (B) TYPE:  amino aci - #d                                                      (C) STRANDEDNESS:  sing - #le                                                  (D) TOPOLOGY:  linear                                                 - -     (ii) MOLECULE TYPE:  peptide                                           - -    (iii) HYPOTHETICAL:  yes                                                - -      (v) FRAGMENT TYPE:  internal fragment                                 - -     (vi) ORIGINAL SOURCE:                                                           (A) ORGANISM:  MDV                                                             (B) STRAIN:  GA                                                       - -     (ix) FEATURE:                                                                   (A) NAME/KEY:  peptide - #of MDV gene US10 polypeptide                         (B) LOCATION:  47 TO - # 139                                                   (D) OTHER INFORMATION: - # peptide homologous to the US10 gene                      polypeptide - #of herpes simplex virus type 1                    - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: - # 9:                           - - Ala Arg Thr Ile Leu Thr Ala Ala Thr Ile Se - #r Gln Ala Ala Met Lys                        5 - #                  - #10                  - #15            - - Ala Gly Lys Pro Pro Ser Ser Arg Leu Trp Gl - #y Glu Ile Phe Asp Arg                    20     - #             25     - #             30                   - - Met Thr Val Thr Leu Asn Glu Tyr Asp Ile Se - #r Ala Ser Pro Phe His                35         - #         40         - #         45                       - - Pro Thr Asp Pro Thr Arg Lys Ile Val Gly Ar - #g Ala Leu Arg Cys Ile            50             - #     55             - #     60                           - - Glu Arg Ala Pro Leu Thr His Glu Glu Met As - #p Thr Arg Phe Thr Ile        65                 - # 70                 - # 75                 - # 80        - - Met Met Tyr Trp Cys Cys Leu Gly His Ala Gl - #y Tyr Cys                                    85 - #                 90                                      - -  - - (2) INFORMATION FOR SEQ ID NO:10:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 91 amino - #acids                                                  (B) TYPE:  amino aci - #d                                                      (C) STRANDEDNESS:  sing - #le                                                  (D) TOPOLOGY:  linear                                                 - -     (ii) MOLECULE TYPE:  peptide                                           - -      (v) FRAGMENT TYPE:  internal fragment                                 - -     (vi) ORIGINAL SOURCE:                                                           (A) ORGANISM:  herpes - #simplex virus type 1 (HSV1)                  - -     (ix) FEATURE:                                                                   (A) NAME/KEY:  peptide - #of HSV1 gene US10 polypeptide                        (B) LOCATION:  192 T - #O 282                                                  (D) OTHER INFORMATION: - # peptide homologous to the US10 gene                      polypeptide - #of MDV                                            - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: - # 10:                          - - Phe Arg Thr Val Val Glu Val Ser Arg Met Cy - #s Ala Ala Asn Val Arg                        5 - #                  - #10                  - #15            - - Asp Pro Pro Pro Pro Ala Thr Gly Ala Met Le - #u Gly Arg His Ala Arg                    20     - #             25     - #             30                   - - Leu Val His Thr Gln Trp Leu Arg Ala Asn Gl - #n Glu Thr Ser Pro Leu                35         - #         40         - #         45                       - - Trp Pro Trp Arg Thr Ala Ala Ile Asn Phe Il - #e Thr Thr Met Ala Pro            50             - #     55             - #     60                           - - Arg Val Gln Thr His Arg His Met His Asp Le - #u Leu Met Ala Cys Ala        65                 - # 70                 - # 75                 - # 80        - - Phe Trp Cys Cys Leu Thr His Ala Ser Thr Cy - #s                                            85 - #                 90                                      - -  - - (2) INFORMATION FOR SEQ ID NO:11:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH:  96 amin - #o acids                                                (B) TYPE:  amino aci - #d                                                      (C) STRANDEDNESS:  sing - #le                                                  (D) TOPOLOGY:  linear                                                 - -     (ii) MOLECULE TYPE:  peptide                                           - -      (v) FRAGMENT TYPE:  internal fragment                                 - -     (vi) ORIGINAL SOURCE:                                                           (A) ORGANISM:  varicell - #a-zoster virus (VZV)                       - -     (ix) FEATURE:                                                                   (A) NAME/KEY:  peptide - #of VZV 64 OR 69 polypeptide                          (B) LOCATION:  41 TO - # 135                                                   (D) OTHER INFORMATION: - # peptide homologous to the US10 gene                    polypeptide of - #herpes simplex virus type 1 OR MDV US10        gene                                                                                          polypeptide                                                        - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: - # 11:                          - - Ala Ala Ala Leu Cys Ala Ile Ser Thr Glu Al - #a Tyr Glu Ala Phe         Ile                                                                                               5 - #                  - #10                  - #15           - - His Ser Pro Ser Glu Arg Pro Cys Ala Ser Le - #u Trp Gly Arg Ala Lys                    20     - #             25     - #             30                   - - Asp Ala Phe Gly Arg Met Cys Gly Glu Leu Al - #a Ala Asp Arg Gln Arg                35         - #         40         - #         45                       - - Pro Pro Ser Val Pro Pro Ile Arg Arg Ala Va - #l Leu Ser Leu Leu Arg            50             - #     55             - #     60                           - - Glu Gln Cys Met Pro Asp Pro Gln Ser His Le - #u Glu Leu Ser Glu Arg        65                 - # 70                 - # 75                 - # 80        - - Leu Ile Leu Met Ala Tyr Trp Cys Cys Leu Gl - #y His Ala Gly Leu Pro                        85 - #                 90 - #                 95               - -  - - (2) INFORMATION FOR SEQ ID NO:12:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH:  95 amin - #o acids                                                (B) TYPE:  amino aci - #d                                                      (C) STRANDEDNESS:  sing - #le                                                  (D) TOPOLOGY:  linear                                                 - -     (ii) MOLECULE TYPE:  peptide                                           - -      (v) FRAGMENT TYPE:  internal fragment                                 - -     (vi) ORIGINAL SOURCE:                                                           (A) ORGANISM:  equine - #herpesvirus type 4 (EHV4)                    - -     (ix) FEATURE:                                                                   (A) NAME/KEY:  peptide - #of EHV4 gene 66 polypeptide                          (B) LOCATION:  80 TO - # 174                                                   (C) OTHER INFORMATION: - # peptide homologous to the US10 gene                      polypeptide - #of herpes simplex virus type 1 OR MDV US10                      gene poly - #peptide                                             - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: - # 12:                          - - Ala Ser Ala Val Arg Ala Met Ser Ala Asp Al - #a Ala Asp Ala Leu Arg                        5 - #                  - #10                  - #15            - - Arg Gly Ala Gly Pro Pro Pro Glu Ile Trp Pr - #o Arg Ala Tyr Arg Met                    20     - #             25     - #             30                   - - Phe Cys Glu Leu Phe Gly Arg Tyr Ala Val Se - #r Pro Met Pro Val Phe                35         - #         40         - #         45                       - - His Ser Ala Asp Pro Leu Arg Arg Ala Val Gl - #y Arg Tyr Leu Val Asp            50             - #     55             - #     60                           - - Leu Gly Ala Ala Pro Val Glu Thr His Ala Gl - #u Leu Ser Thr Arg Leu        65                 - # 70                 - # 75                 - # 80        - - Leu Phe Cys Ala His Trp Cys Cys Leu Gly Hi - #s Ala Phe Gly Cys                            85 - #                 90 - #                 95               - -  - - (2) INFORMATION FOR SEQ ID NO:13:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH:  92 amin - #o acids                                                (B) TYPE:  amino aci - #d                                                      (C) STRANDEDNESS:  sing - #le                                                  (D) TOPOLOGY:  linear                                                 - -     (ii) MOLECULE TYPE:  peptide                                           - -    (iii) HYPOTHETICAL:  yes                                                - -      (v) FRAGMENT TYPE:  N-terminal fragme - #nt                           - -     (vi) ORIGINAL SOURCE:                                                           (A) ORGANISM:  MDV                                                             (B) STRAIN:  GA                                                       - -     (ix) FEATURE:                                                                   (A) NAME/KEY: peptide o - #f MDV gene US2 polypeptide                          (B) LOCATION:  1 TO - #92                                                      (D) OTHER INFORMATION: - # peptide homologous to the US2 gene                       polypeptide - #of herpes simplex virus type 1                    - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: - # 13:                          - - Met Gly Val Ser Met Ile Thr Ile Val Thr Le - #u Leu Asp Glu Cys Asp                        5 - #                  - #10                  - #15            - - Arg Leu Pro Gly Arg Ser Arg Asp Ala Ala Se - #r Thr Leu Trp Ile Phe                    20     - #             25     - #             30                   - - Leu Ile Lys Gln Cys Met Glu Gln Ile Gln As - #p Asp Val Gly Val Pro                35         - #         40         - #         45                       - - Ile Ile Ala Arg Ala Ala Asp Leu Phe Arg Ph - #e Ala Lys Pro Met Leu            50             - #     55             - #     60                           - - Ile Leu Pro Arg Gln His Arg Pro Ile Val Ar - #g Thr Lys Pro Pro Asp       65                  - # 70                 - # 75                 - # 80        - - Gly Thr Gly Val Arg Gly Thr Gly Leu Ala Gl - #y Thr                                        85 - #                 90                                      - -  - - (2) INFORMATION FOR SEQ ID NO:14:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH:  92 amin - #o acids                                                (B) TYPE:  amino aci - #d                                                      (C) STRANDEDNESS:  sing - #le                                                  (D) TOPOLOGY:  linear                                                 - -     (ii) MOLECULE TYPE:  peptide                                           - -      (v) FRAGMENT TYPE:  N-terminal fragme - #nt                           - -     (vi) ORIGINAL SOURCE:                                                           (A) ORGANISM:  herpes - #simplex virus type 1 (HSV1)                  - -     (ix) FEATURE:                                                                   (A) NAME/KEY:  peptide - #of HSV1 gene US2 polypeptide                         (B) LOCATION:  1 TO - #92                                                      (D) OTHER INFORMATION: - # peptide homologous to the US2 gene                       polypeptide - #of MDV                                            - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: - # 14:                          - - Met Gly Val Val Val Val Asn Val Met Thr Le - #u Leu Asp Gln Asn Asn                        5 - #                  - #10                  - #15            - - Ala Leu Pro Arg Thr Ser Val Asp Ala Ser Pr - #o Ala Leu Trp Ser Phe                    20     - #             25     - #             30                   - - Leu Leu Arg Gln Cys Arg Ile Leu Ala Ser Gl - #u Pro Leu Gly Thr Pro                35         - #         40         - #         45                       - - Val Val Val Arg Pro Ala Asn Leu Arg Arg Le - #u Ala Glu Pro Leu Met            50             - #    55              - #    60                            - - Asp Leu Pro Lys Pro Thr Arg Pro Ile Val Ar - #g Thr Arg Ser Cys Arg       65                  - #70                  - #75                  - # 80        - - Cys Pro Pro Asn Thr Thr Thr Gly Leu Phe Al - #a Glu                                        85 - #                 90                                      - -  - - (2) INFORMATION FOR SEQ ID NO:15:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH:  98 amin - #o acids                                                (B) TYPE:  amino aci - #d                                                      (C) STRANDEDNESS:  sing - #le                                                  (D) TOPOLOGY:  linear                                                 - -     (ii) MOLECULE TYPE:  peptide                                           - -      (v) FRAGMENT TYPE:  N-terminal fragme - #nt                           - -     (vi) ORIGINAL SOURCE:                                                           (A) ORGANISM:  pseudora - #bies virus (PRV)                           - -     (ix) FEATURE:                                                                   (A) NAME/KEY:  peptide - #of PRV US2 polypeptide                               (B) LOCATION: 1 to 9 - #8                                                      (D) OTHER INFORMATION: - # peptide homologous to the US2 gene                     polypeptide of - #herpes simplex virus type 1 OR MDV US 2        gene                                                                                          polypeptide                                                        - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: - # 15:                          - - Met Gly Val Thr Ala Ile Thr Val Val Thr Le - #u Met Asp Gly Ser         Gly                                                                                               5 - #                  - #10                  - #15           - - Arg Ile Pro Ala Phe Val Gly Glu Ala His Pr - #o Asp Leu Trp Lys Val                    20     - #             25     - #             30                   - - Leu Thr Glu Trp Cys Tyr Ala Ser Leu Val Gl - #n Gln Arg Arg Ala Ala                35         - #         40         - #         45                       - - Asp Glu Asp Thr Pro Arg Gln His Val Val Le - #u Arg Ser Ser Glu Ile            50             - #     55             - #     60                           - - Ala Pro Gly Ser Leu Ala Leu Leu Pro Arg Al - #a Thr Arg Pro Val Val        65                 - # 70                 - # 75                 - # 80        - - Arg Thr Arg Ser Asp Pro Thr Ala Pro Phe Ty - #r Ile Thr Thr Glu Thr                        85 - #                 90 - #                 95               - - His Glu                                                                    - -  - - (2) INFORMATION FOR SEQ ID NO:16:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH:  100 ami - #no acids                                               (B) TYPE:  amino aci - #d                                                      (C) STRANDEDNESS:  sing - #le                                                  (D) TOPOLOGY:  linear                                                 - -     (ii) MOLECULE TYPE:  peptide                                           - -    (iii) HYPOTHETICAL:  yes                                                - -      (v) FRAGMENT TYPE:  internal fragment                                 - -     (vi) ORIGINAL SOURCE:                                                           (A) ORGANISM:  MDV                                                             (B) STRAIN:  GA                                                       - -     (ix) FEATURE:                                                                   (A) NAME/KEY:  peptide - #of MDV gene US3 polypeptide                          (B) LOCATION:  179 T - #O 278                                                  (D) OTHER INFORMATION: - # peptide homologous to the US3 gene                       polypeptide - #of herpes simplex virus type 1                    - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: - # 16:                          - - Gly Pro Leu Pro Leu Asn Gln Ile Ile Thr Il - #e Glu Arg Gly Leu Leu                        5 - #                  - #10                  - #15            - - Gly Ala Leu Ala Tyr Ile His Glu Lys Gly Il - #e Ile His Arg Asp Val                    20     - #             25     - #             30                   - - Lys Thr Glu Asn Ile Phe Leu Asp Lys Pro Gl - #u Asn Val Val Leu Gly                35         - #         40         - #         45                       - - Asp Phe Gly Ala Ala Cys Lys Leu Asp Glu Hi - #s Thr Asp Lys Pro Lys            50             - #     55             - #     60                           - - Cys Tyr Gly Trp Ser Gly Thr Leu Glu Thr As - #n Ser Pro Glu Leu Leu        65                 - # 70                 - # 75                 - # 80        - - Ala Leu Asp Pro Tyr Cys Thr Lys Thr Asp Il - #e Trp Ser Ala Gly Leu                        85 - #                 90 - #                 95               - - Val Leu Phe Glu                                                                       100                                                                 - -  - - (2) INFORMATION FOR SEQ ID NO:17:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 100 amino - #acids                                                 (B) TYPE:  amino aci - #d                                                      (C) STRANDEDNESS:  sing - #le                                                  (D) TOPOLOGY:  linear                                                 - -     (ii) MOLECULE TYPE:  peptide                                           - -      (v) FRAGMENT TYPE:  internal fragment                                 - -     (vi) ORIGINAL SOURCE:                                                           (A) ORGANISM:  herpes - #simplex virus type 1 (HSV1)                  - -     (ix) FEATURE:                                                                   (A) NAME/KEY:  peptide - #of HSV1 serine/threonine-                                 protein k - #inase                                                        (B) LOCATION:  275 T - #O 374                                                  (D) OTHER INFORMATION: - # peptide homologous to the US3 gene                       polypeptide - #of MDV                                            - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: - # 17:                          - - Asn Pro Leu Gly Arg Pro Gln Ile Ala Ala Va - #l Ser Arg Gln Leu Leu                        5 - #                  - #10                  - #15            - - Ser Ala Val Asp Tyr Ile His Arg Gln Gly Il - #e Ile His Arg Asp Ile                    20     - #             25     - #             30                   - - Lys Thr Glu Asn Ile Phe Ile Asn Thr Pro Gl - #u Asp Ile Cys Leu Gly                35         - #         40         - #         45                       - - Asp Phe Gly Ala Ala Cys Phe Val Gln Gly Se - #r Arg Ser Ser Pro Phe            50             - #     55             - #     60                           - - Pro Tyr Gly Ile Ala Gly Thr Ile Asp Thr As - #n Ala Pro Glu Val Leu        65                 - # 70                 - # 75                 - # 80        - - Ala Gly Asp Pro Tyr Thr Thr Thr Val Asp Il - #e Trp Ser Ala Gly Leu                        85 - #                 90 - #                 95               - - Val Ile Phe Glu                                                                       100                                                                 - -  - - (2) INFORMATION FOR SEQ ID NO:18:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH:  98 amin - #o acids                                                (B) TYPE:  amino aci - #d                                                      (C) STRANDEDNESS:  sing - #le                                                  (D) TOPOLOGY:  linear                                                 - -     (ii) MOLECULE TYPE:  peptide                                           - -      (v) FRAGMENT TYPE:  internal fragment                                 - -     (vi) ORIGINAL SOURCE:                                                           (A) ORGANISM:  varicell - #a-zoster virus (VZV)                       - -     (ix) FEATURE:                                                                   (A) NAME/KEY:  peptide - #of VZV serine/threonine-protein           kinase                                                                                     (B) LOCATION:  177 T - #O 274                                                  (D) OTHER INFORMATION: - #peptide homologous to serine/threoni     ne-                                                                                            protein k - #inase of herpes simplex virus type 1 OR US3       - #gene                                                                                         polypeptide - #of MDV                                            - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: - # 18:                          - - Asn Leu Pro Ile Cys Asp Ile Leu Ala Ile Gl - #n Arg Ser Val Leu         Arg                                                                                               5 - #                  - #10                  - #15           - - Ala Leu Gln Tyr Leu His Asn Asn Ser Ile Il - #e His Arg Asp Ile Lys                    20     - #             25     - #             30                   - - Ser Glu Asn Ile Phe Ile Asn His Pro Gly As - #p Val Cys Val Gly Asp                35         - #         40         - #         45                       - - Phe Gly Ala Ala Cys Phe Pro Val Asp Ile As - #n Ala Asn Arg Tyr Tyr            50             - #     55             - #     60                           - - Gly Trp Ala Gly Thr Ile Ala Thr Asn Ser Pr - #o Glu Leu Leu Ala Arg        65                 - # 70                 - # 75                 - # 80        - - Asp Pro Tyr Gly Pro Ala Val Asp Ile Trp Se - #r Ala Gly Ile Val Leu                        85 - #                 90 - #                 95               - - Phe Glu                                                                    - -  - - (2) INFORMATION FOR SEQ ID NO:19:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH:  97 amin - #o acids                                                (B) TYPE:  amino aci - #d                                                      (C) STRANDEDNESS:  sing - #le                                                  (D) TOPOLOGY:  linear                                                 - -     (ii) MOLECULE TYPE:  peptide                                           - -      (v) FRAGMENT TYPE:  internal fragment                                 - -     (vi) ORIGINAL SOURCE:                                                           (A) ORGANISM:  pseudora - #bies virus (PRV)                           - -     (ix) FEATURE:                                                                   (A) NAME/KEY:  peptide - #of PRV serine/threonine-protein                           kinase                                                                    (B) LOCATION:  193 T - #O 289                                                  (D) OTHER INFORMATION:pept - #ide homologous to the serine/                        threonine pro - #tein kinase of herpes simplex virus                           type 1 OR - #the US3 gene polypeptide of MDV                      - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: - # 19:                          - - Gly Pro Leu Asp Met Arg Asp Ala Gly Arg Va - #l Ile Arg Ser Val Leu                        5 - #                  - #10                  - #15            - - Arg Gly Leu Ala Tyr Leu His Gly Met Arg Il - #e Met His Arg Asp Val                    20     - #             25     - #             30                   - - Lys Ala Glu Asn Ile Phe Leu Glu Asp Val As - #p Thr Val Cys Leu Gly                35         - #         40         - #         45                       - - Asp Leu Gly Ala Ala Arg Cys Asn Val Ala Al - #a Pro Asn Phe Tyr Gly            50             - #     55             - #     60                           - - Leu Ala Gly Thr Ile Glu Thr Asn Ala Pro Gl - #u Val Leu Ala Arg Asp        65                 - # 70                 - # 75                 - # 80        - - Arg Tyr Asp Thr Lys Val Asp Val Trp Gly Al - #a Gly Val Val Leu Phe                        85 - #                 90 - #                 95               - - Glu                                                                        - -  - - (2) INFORMATION FOR SEQ ID NO:20:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH:  98 amin - #o acids                                                (B) TYPE:  amino aci - #d                                                      (C) STRANDEDNESS:  sing - #le                                                  (D) TOPOLOGY:  linear                                                 - -     (ii) MOLECULE TYPE:  peptide                                           - -    (iii) HYPOTHETICAL:  yes                                                - -      (v) FRAGMENT TYPE:  internal fragment                                 - -     (vi) ORIGINAL SOURCE:                                                           (A) ORGANISM:  MDV                                                             (B) STRAIN:  GA                                                       - -     (ix) FEATURE:                                                                   (A) NAME/KEY: peptide o - #f MDV gene US6 polypeptide                          (B) LOCATION:  114 T - #O 211                                                  (D) OTHER INFORMATION:pept - #ide homologous to the gD              polypeptide                                                                                    of herpes - #simplex virus type 1                                 - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: - # 20:                          - - Tyr Asp Ala Leu Val Ala Trp Phe Val Leu Gl - #y Arg Ala Cys Gly         Arg                                                                                               5 - #                  - #10                  - #15           - - Pro Ile Tyr Leu Arg Glu Tyr Ala Asn Cys Se - #r Thr Asn Glu Pro Phe                    20     - #             25     - #             30                   - - Gly Thr Cys Lys Leu Lys Ser Leu Gly Trp Tr - #p Asp Arg Arg Tyr Ala                35         - #         40         - #         45                       - - Met Thr Ser Tyr Ile Asp Arg Asp Glu Leu Ly - #s Leu Ile Ile Ala Ala            50             - #     55             - #     60                           - - Pro Ser Arg Glu Leu Ser Gly Leu Tyr Thr Ar - #g Leu Ile Ile Ile Asn        65                 - # 70                 - # 75                 - # 80        - - Gly Glu Pro Ile Ser Ser Asp Ile Leu Leu Th - #r Val Lys Gly Thr Cys                        85 - #                 90 - #                 95               - - Ser Phe                                                                    - -  - - (2) INFORMATION FOR SEQ ID NO:21:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH:  99 amin - #o acids                                                (B) TYPE:  amino aci - #d                                                      (C) STRANDEDNESS:  sing - #le                                                  (D) TOPOLOGY:  linear                                                 - -     (ii) MOLECULE TYPE:  peptide                                           - -      (v) FRAGMENT TYPE:  internal fragment                                 - -     (vi) ORIGINAL SOURCE:                                                           (A) ORGANISM:  herpes - #simplex virus type 1 (HSV1)                  - -     (ix) FEATURE:                                                                   (A) NAME/KEY:  peptide - #of HSV1 gD polypeptide                               (B) LOCATION:  118 T - #O 216                                                  (D) OTHER INFORMATION: - # peptide homologous to the US6 gene                       polypeptide - #of MDV                                            - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: - # 21:                          - - Tyr Asn Leu Thr Ile Ala Trp Phe Arg Met Gl - #y Gly Asn Cys Ala Ile                        5 - #                  - #10                  - #15            - - Pro Ile Thr Val Met Glu Tyr Thr Glu Cys Se - #r Tyr Asn Lys Ser Leu                    20     - #             25     - #             30                   - - Gly Ala Cys Pro Ile Arg Thr Gln Pro Arg Tr - #p Asn Tyr Tyr Asp Ser                35         - #         40         - #         45                       - - Phe Ser Ala Val Ser Glu Asp Asn Leu Gly Ph - #e Leu Met His Ala Pro            50             - #     55             - #     60                           - - Ala Phe Glu Thr Ala Gly Thr Tyr Leu Arg Le - #u Val Lys Ile Asn Asp        65                 - # 70                 - # 75                 - # 80        - - Trp Thr Glu Ile Thr Gln Phe Ile Leu Glu Hi - #s Arg Ala Lys Gly Ser                        85 - #                 90 - #                 95               - - Cys Lys Tyr                                                                - -  - - (2) INFORMATION FOR SEQ ID NO:22:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 100 amino - #acids                                                 (B) TYPE:  amino aci - #d                                                      (C) STRANDEDNESS:  sing - #le                                                  (D) TOPOLOGY:  linear                                                 - -     (ii) MOLECULE TYPE:  peptide                                           - -      (v) FRAGMENT TYPE:  internal fragment                                 - -     (vi) ORIGINAL SOURCE:                                                           (A) ORGANISM:  pseudora - #bies virus (PRV)                           - -     (ix) FEATURE:                                                                   (A) NAME/KEY:  peptide - #of PRV gp50 polypeptide                              (B) LOCATION:  92 TO - # 191                                                   (D) OTHER INFORMATION: - #peptide homologous to gD of herpes                        simplex v - #irus type 1 OR US6 gene polypeptide of MDV          - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: - # 22:                          - - Tyr Arg Ala His Val Ala Trp Tyr Arg Ile Al - #a Asp Gly Cys Ala His                        5 - #                  - #10                  - #15            - - Leu Leu Tyr Phe Ile Glu Tyr Ala Asp Cys As - #p Pro Arg Gln Val Phe                    20     - #             25     - #             30                   - - Gly Arg Cys Arg Arg Arg Thr Thr Pro Met Tr - #p Trp Thr Pro Ser Ala                35         - #         40         - #         45                       - - Asp Tyr Met Phe Pro Thr Glu Asp Glu Leu Gl - #y Leu Leu Met Val Ala            50             - #     55             - #     60                           - - Pro Gly Arg Phe Asn Glu Gly Gln Tyr Arg Ar - #g Leu Val Ser Val Asp       65                  - # 70                 - # 75                 - # 80        - - Gly Val Asn Ile Leu Thr Asp Phe Met Val Al - #a Leu Pro Glu Gly Gln                        85 - #                 90 - #                 95               - - Glu Cys Pro Phe                                                                       100                                                                 - -  - - (2) INFORMATION FOR SEQ ID NO:23:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH:  99 amin - #o acids                                                (B) TYPE:  amino aci - #d                                                      (C) STRANDEDNESS:  sing - #le                                                  (D) TOPOLOGY:  linear                                                 - -     (ii) MOLECULE TYPE:  peptide                                           - -      (v) FRAGMENT TYPE:  internal fragment                                 - -     (vi) ORIGINAL SOURCE:                                                           (A) ORGANISM:  equine - #herpesvirus type 1 (EHV1)                    - -     (ix) FEATURE:                                                                   (A) NAME/KEY:  peptide - #of EHV1 gD polypeptide                               (B) LOCATION:  113 T - #O 211                                                  (D) OTHER INFORMATION: - #peptide homologous to gD of herpes                        simplex v - #irus type 1 OR US6 gene polypeptide of MDV          - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: - # 23:                          - - Tyr Ser Ala Arg Leu Thr Trp Phe Lys Ile Me - #t Pro Thr Cys Ala Thr                        5 - #                  - #10                  - #15            - - Pro Ile His Asp Val Ser Tyr Met Lys Cys As - #n Pro Lys Leu Ser Phe                    20     - #             25     - #             30                   - - Ala Met Cys Asp Glu Arg Ser Asp Ile Leu Tr - #p Gln Ala Ser Leu Ile                35         - #         40         - #         45                       - - Thr Met Ala Ala Glu Thr Asp Asp Glu Leu Gl - #y Leu Val Leu Ala Ala            50             - #     55             - #     60                           - - Pro Ala His Ser Ala Ser Gly Leu Tyr Arg Ar - #g Val Ile Glu Ile Asp        65                 - # 70                 - # 75                 - # 80        - - Gly Arg Arg Ile Tyr Thr Asp Phe Ser Val Th - #r Ile Pro Ser Glu Arg                        85 - #                 90 - #                 95               - - Cys Pro Ile                                                                - -  - - (2) INFORMATION FOR SEQ ID NO:24:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH:  99 amin - #o acids                                                (B) TYPE:  amino aci - #d                                                      (C) STRANDEDNESS:  sing - #le                                                  (D) TOPOLOGY:  linear                                                 - -     (ii) MOLECULE TYPE:  peptide                                           - -      (v) FRAGMENT TYPE:  internal fragment                                 - -     (vi) ORIGINAL SOURCE:                                                           (A) ORGANISM:  bovine - #herpesvirus type 1 (BHV1)                    - -     (ix) FEATURE:                                                                   (A) NAME/KEY:  peptide - #of BHV1 gD polypeptide                               (B) LOCATION:  101 T - #O 199                                                  (D) OTHER INFORMATION: - #peptide homologous to gD of herpes                        simplex v - #irus type 1 OR US6 gene polypeptide of MDV          - -     (xi) SEQUENCE DESCRIPTION:  SEQ ID NO: - # 24:                         - - Tyr Asn Ala Thr Val Ile Trp Tyr Lys Ile Gl - #u Ser Gly Cys Ala Arg                        5 - #                  - #10                  - #15            - - Pro Leu Tyr Tyr Met Glu Tyr Thr Glu Cys Gl - #u Pro Arg Lys His Phe                    20     - #             25     - #             30                   - - Gly Tyr Cys Arg Tyr Arg Thr Pro Pro Phe Tr - #p Asp Ser Phe Leu Ala                35         - #         40         - #         45                       - - Gly Phe Ala Tyr Pro Thr Asp Asp Glu Leu Gl - #y Leu Ile Met Ala Ala            50             - #     55             - #     60                           - - Pro Ala Arg Leu Val Glu Gly Gln Tyr Arg Ar - #g Ala Leu Tyr Ile Asp        65                 - # 70                 - # 75                 - # 80        - - Gly Thr Val Ala Tyr Thr Asp Phe Met Val Tr - #p Leu Pro Ala Gly Asp                        85 - #                 90 - #                 95               - - Cys Trp Phe                                                                - -  - - (2) INFORMATION FOR SEQ ID NO:25:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH:  97 amin - #o acids                                                (B) TYPE:  amino aci - #d                                                      (C) STRANDEDNESS:  sing - #le                                                  (D) TOPOLOGY:  linear                                                 - -     (ii) MOLECULE TYPE:  peptide                                           - -    (iii) HYPOTHETICAL:  yes                                                - -      (v) FRAGMENT TYPE:  internal fragment                                 - -     (vi) ORIGINAL SOURCE:                                                           (A) ORGANISM:  MDV                                                             (B) STRAIN:  GA                                                       - -     (ix) FEATURE:                                                                   (A) NAME/KEY: peptide o - #f MDV gene US7 polypeptide                          (B) LOCATION:  47 TO - # 143                                                   (D) OTHER INFORMATION: - #peptide homologous to the gI                              polypeptide - #of herpes simplex virus type 1                    - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: - # 25:                          - - Val Arg Gly Gln Leu Leu Phe Leu Gly Asp Gl - #n Thr Arg Thr Ser Ser                        5 - #                  - #10                  - #15            - - Tyr Thr Gly Thr Thr Glu Ile Leu Lys Trp As - #p Glu Glu Tyr Lys Cys                    20     - #             25     - #             30                   - - Tyr Ser Val Leu His Ala Thr Ser Tyr Met As - #p Cys Pro Ala Ile Asp                35         - #         40         - #         45                       - - Ala Thr Val Phe Arg Gly Cys Arg Asp Ala Va - #l Val Tyr Ala Gln Pro            50             - #     55             - #     60                           - - His Gly Arg Val Gln Pro Phe Pro Glu Lys Gl - #y Thr Leu Leu Arg Ile        65                 - # 70                 - # 75                 - # 80        - - Val Glu Pro Arg Val Ser Asp Thr Gly Ser Ty - #r Tyr Ile Arg Val Ser                        85 - #                 90 - #                 95               - - Leu                                                                        - -  - - (2) INFORMATION FOR SEQ ID NO:26:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH:  99 amin - #o acids                                                (B) TYPE:  amino aci - #d                                                      (C) STRANDEDNESS:  sing - #le                                                  (D) TOPOLOGY:  linear                                                 - -     (ii) MOLECULE TYPE:  peptide                                           - -      (v) FRAGMENT TYPE:  internal fragment                                 - -     (vi) ORIGINAL SOURCE:                                                           (A) ORGANISM:  herpes - #simplex virus type 1 (HSV1)                  - -     (ix) FEATURE:                                                                   (A) NAME/KEY:  peptide - #of HSV1 gI polypeptide                               (B) LOCATION:  53 TO - # 151                                                   (D) OTHER INFORMATION: - # peptide homologous to the US7 gene                       polypeptide - #of MDV                                            - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: - # 26:                          - - Ile Leu Gly Glu Leu Arg Phe Val Gly Asp Gl - #n Val Pro His Thr Thr                        5 - #                  - #10                  - #15            - - Tyr Tyr Asp Gly Gly Val Glu Leu Trp His Ty - #r Pro Met Gly His Lys                    20     - #             25     - #             30                   - - Cys Pro Arg Val Val His Val Val Thr Val Th - #r Ala Cys Pro Arg Arg                35         - #         40         - #         45                       - - Pro Ala Val Ala Phe Ala Leu Cys Arg Ala Th - #r Asp Ser Thr His Ser            50             - #     55             - #     60                           - - Pro Ala Tyr Pro Thr Leu Glu Leu Asn Leu Al - #a Gln Gln Pro Leu Leu        65                 - # 70                 - # 75                 - # 80        - - Arg Val Gln Arg Ala Thr Arg Asp Tyr Ala Gl - #y Val Tyr Val Leu Arg                        85 - #                 90 - #                 95               - - Val Trp Val                                                                - -  - - (2) INFORMATION FOR SEQ ID NO:27:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH:  100 ami - #no acids                                               (B) TYPE:  amino aci - #d                                                      (C) STRANDEDNESS:  sing - #le                                                  (D) TOPOLOGY:  linear                                                 - -     (ii) MOLECULE TYPE:  peptide                                           - -      (v) FRAGMENT TYPE:  internal fragment                                 - -     (vi) ORIGINAL SOURCE:                                                           (A) ORGANISM:  varicell - #a-zoster virus (VZV)                       - -     (ix) FEATURE:                                                                   (A) NAME/KEY:  peptide - #of VZV gI polypeptide                                (B) LOCATION:  51 TO - # 150                                                   (D) OTHER INFORMATION: - #peptide homologous to gI of herpes                        simplex v - #irus type 1 OR US7 gene polypeptide of MDV          - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: - # 27:                          - - Ile Lys Gly Gln Leu Val Phe Ile Gly Glu Gl - #n Leu Pro Thr Gly Thr                        5 - #                  - #10                  - #15            - - Asn Tyr Ser Gly Thr Leu Glu Leu Leu Tyr Al - #a Asp Thr Val Ala Phe                    20     - #             25     - #             30                   - - Cys Phe Arg Ser Val Gln Val Ile Arg Tyr As - #p Gly Cys Pro Arg Ile                35         - #         40         - #         45                       - - Arg Thr Ser Ala Phe Ile Ser Cys Arg Tyr Ly - #s His Ser Trp His Tyr            50             - #     55             - #     60                           - - Gly Asn Ser Thr Asp Arg Ile Ser Thr Glu Pr - #o Asp Ala Gly Val Met       65                  - # 70                 - # 75                 - # 80        - - Leu Lys Ile Thr Lys Pro Gly Ile Asn Asp Al - #a Gly Val Tyr Val Leu                        85 - #                 90 - #                 95               - - Leu Val Arg Leu                                                                       100                                                                 - -  - - (2) INFORMATION FOR SEQ ID NO:28:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH:  94 amin - #o acids                                                (B) TYPE:  amino aci - #d                                                      (C) STRANDEDNESS:  sing - #le                                                  (D) TOPOLOGY:  linear                                                 - -     (ii) MOLECULE TYPE:  peptide                                           - -      (v) FRAGMENT TYPE:  internal fragment                                 - -     (vi) ORIGINAL SOURCE:                                                           (A) ORGANISM:  pseudora - #bies virus (PRV)                           - -     (ix) FEATURE:                                                                   (A) NAME/KEY:  peptide - #of PRV gp53 polypeptide                              (B) LOCATION:  59 TO - # 152                                                   (D) OTHER INFORMATION: - #peptide homologous to gI of herpes                        simplex v - #irus type 1 OR US7 gene polypeptide of MDV          - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: - # 28:                          - - Ile Asp Gly Thr Leu Leu Phe Leu Glu Gly Pr - #o Ser Pro Ser Asn Tyr                        5 - #                  - #10                  - #15            - - Ser Gly Arg Val Glu Leu Leu Arg Leu Asp Pr - #o Lys Arg Ala Cys Tyr                    20     - #             25     - #             30                   - - Thr Arg Glu Tyr Ala Ala Glu Tyr Asp Leu Cy - #s Pro Arg Val His His                35         - #         40         - #         45                       - - Glu Ala Phe Arg Gly Cys Leu Arg Lys Arg Gl - #u Pro Leu Ala Arg Arg            50             - #     55             - #     60                           - - Ala Ser Ala Ala Val Glu Ala Arg Arg Leu Le - #u Phe Val Ser Arg Pro        65                 - # 70                 - # 75                 - # 80        - - Ala Pro Pro Asp Ala Gly Ser Tyr Val Leu Ar - #g Val Arg Val                                85 - #                 90                                      - -  - - (2) INFORMATION FOR SEQ ID NO:29:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH:  99 amin - #o acids                                                (B) TYPE:  amino aci - #d                                                      (C) STRANDEDNESS:  sing - #le                                                  (D) TOPOLOGY:  linear                                                 - -     (ii) MOLECULE TYPE:  peptide                                           - -      (v) FRAGMENT TYPE:  internal fragment                                 - -     (vi) ORIGINAL SOURCE:                                                           (A) ORGANISM:  equine - #herpesvirus type 1 (EHV1)                    - -     (ix) FEATURE:                                                                   (A) NAME/KEY:  peptide - #of EHV1 gI polypeptide                               (B) LOCATION:  51 TO - # 149                                                   (D) OTHER INFORMATION: - # peptide homologous to gI of herpes                        simplex - #virus type 1 OR US7 gene polypeptide of MDV          - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: - # 29:                          - - Leu Val Gly His Leu Leu Phe Leu Asp Gly Gl - #n Arg Leu Pro Thr Thr                        5 - #                  - #10                  - #15            - - Asn Tyr Ser Gly Leu Ile Glu Leu Ile His Ty - #r Asn Tyr Ser Ser Val                    20     - #             25     - #             30                   - - Cys Tyr Thr Val Ile Gln Thr Ile Ser Tyr Gl - #u Ser Cys Pro Arg Val                35         - #         40         - #         45                       - - Ala Asn Asn Ala Phe Arg Ser Cys Leu His Ly - #s Thr Ser Lys His Tyr            50             - #     55             - #     60                           - - His Asp Tyr Phe Arg Val Asn Ala Ser Val Gl - #u Thr Asn Val Leu Leu        65                 - # 70                 - # 75                 - # 80        - - Asn Ile Thr Lys Pro Gln Pro Thr Asp Ser Gl - #y Ala Tyr Ile Leu Arg                        85 - #                 90 - #                 95               - - Val Lys Leu                                                                - -  - - (2) INFORMATION FOR SEQ ID NO:30:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH:  95 amin - #o acids                                                (B) TYPE:  amino aci - #d                                                      (C) STRANDEDNESS:  sing - #le                                                  (D) TOPOLOGY:  linear                                                 - -     (ii) MOLECULE TYPE:  peptide                                           - -    (iii) HYPOTHETICAL:  yes                                                - -      (v) FRAGMENT TYPE:  internal fragment                                 - -     (vi) ORIGINAL SOURCE:                                                           (A) ORGANISM:  MDV                                                             (B) STRAIN:  GA                                                       - -     (ix) FEATURE:                                                                   (A) NAME/KEY: peptide o - #f MDV gene US8 polypeptide                          (B) LOCATION:  232 T - #O 326                                                  (D) OTHER INFORMATION: - # peptide homologous to the gE                             polypeptide - #of herpes simplex virus type 1                    - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: - # 30:                          - - Cys Lys Phe Val Thr Ile Tyr Glu Pro Cys Il - #e Phe His Pro Lys Glu                        5 - #                  - #10                  - #15            - - Pro Glu Cys Ile Thr Thr Ala Glu Gln Ser Va - #l Cys His Phe Ala Ser                    20     - #             25     - #             30                   - - Asn Ile Asp Ile Leu Gln Ile Ala Ala Ala Ar - #g Ser Glu Asn Cys Ser                35         - #         40         - #         45                       - - Thr Gly Tyr Arg Arg Cys Ile Tyr Asp Thr Al - #a Ile Asp Glu Ser Val            50             - #     55             - #     60                           - - Gln Ala Arg Leu Thr Phe Ile Glu Pro Gly Il - #e Pro Ser Phe Lys Met       65                  - # 70                 - # 75                 - # 80        - - Lys Asp Val Gln Val Asp Asp Ala Gly Leu Ty - #r Val Val Val Ala                            85 - #                 90 - #                 95               - -  - - (2) INFORMATION FOR SEQ ID NO:31:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH:  91 amin - #o acids                                                (B) TYPE:  amino aci - #d                                                      (C) STRANDEDNESS:  sing - #le                                                  (D) TOPOLOGY:  linear                                                 - -     (ii) MOLECULE TYPE:  peptide                                           - -      (v) FRAGMENT TYPE:  internal fragment                                 - -     (vi) ORIGINAL SOURCE:                                                           (A) ORGANISM:  herpes - #simplex virus type 1 (HSV1)                  - -     (ix) FEATURE:                                                                   (A) NAME/KEY:  peptide - #of HSV1 gE polypeptide                               (B) LOCATION:  271 t - #o 361                                                  (D) OTHER INFORMATION: - # peptide homologous to the US8 gene                       polypeptide - #of MDV                                            - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: - # 31:                          - - Cys Ala Glu Met Arg Ile Tyr Glu Ser Cys Le - #u Tyr His Pro Gln Leu                        5 - #                  - #10                  - #15            - - Pro Glu Cys Leu Ser Pro Ala Asp Ala Pro Cy - #s Ala Ala Ser Thr Trp                    20     - #             25     - #             30                   - - Thr Ser Arg Leu Ala Val Arg Ser Tyr Ala Gl - #y Cys Ser Arg Thr Asn                35         - #         40         - #         45                       - - Pro Pro Pro Arg Cys Ser Ala Glu Ala His Me - #t Glu Pro Val Pro Gly            50             - #     55             - #     60                           - - Leu Ala Trp Gln Ala Ala Ser Val Asn Leu Gl - #u Phe Arg Asp Ala Ser        65                 - # 70                 - # 75                 - # 80        - - Pro Gln His Ser Gly Leu Tyr Leu Cys Val Va - #l                                            85 - #                 90                                      - -  - - (2) INFORMATION FOR SEQ ID NO:32:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH:  94 amin - #o acids                                                (B) TYPE:  amino aci - #d                                                      (C) STRANDEDNESS:  sing - #le                                                  (D) TOPOLOGY:  linear                                                 - -     (ii) MOLECULE TYPE:  peptide                                           - -      (v) FRAGMENT TYPE:  internal fragment                                 - -     (vi) ORIGINAL SOURCE:                                                           (A) ORGANISM:  varicell - #a-zoster virus (VZV)                       - -     (ix) FEATURE:                                                                   (A) NAME/KEY:  peptide - #of VZV gE polypeptide                                (B) LOCATION:  387 T - #O 480                                                  (D) OTHER INFORMATION: - # peptide homologous to gE of herpes                       simplex v - #irus type 1 OR US8 gene polypeptide of MDV          - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: - # 32:                          - - Cys Gln Pro Met Arg Leu Tyr Ser Thr Cys Le - #u Tyr His Pro Asn Ala                        5 - #                  - #10                  - #15            - - Pro Gln Cys Leu Ser His Met Asn Ser Gly Cy - #s Thr Phe Thr Ser Pro                    20     - #             25     - #             30                   - - His Leu Ala Gln Arg Val Ala Ser Thr Val Ty - #r Gln Asn Cys Glu His                35         - #         40         - #         45                       - - Ala Asp Asn Tyr Thr Ala Tyr Cys Leu Gly Il - #e Ser His Met Glu Pro            50             - #     55             - #     60                           - - Ser Phe Gly Leu Ile Leu His Asp Gly Gly Th - #r Thr Leu Lys Phe Val        65                 - # 70                 - # 75                 - # 80        - - Asp Thr Pro Glu Ser Leu Ser Gly Leu Tyr Va - #l Phe Val Val                                85 - #                 90                                      - -  - - (2) INFORMATION FOR SEQ ID NO:33:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH: 83 amino - #acids                                                  (B) TYPE:  amino aci - #d                                                      (C) STRANDEDNESS:  sing - #le                                                  (D) TOPOLOGY:  linear                                                 - -     (ii) MOLECULE TYPE:  peptide                                           - -      (v) FRAGMENT TYPE:  internal fragment                                 - -     (vi) ORIGINAL SOURCE:                                                           (A) ORGANISM:  pseudora - #bies virus (PRV)                           - -     (ix) FEATURE:                                                                   (A) NAME/KEY:  peptide - #of PRV gI polypeptide                                (B) LOCATION:  274 T - #O 356                                                  (D) OTHER INFORMATION: - # peptide homologous to gE of herpes                       simplex v - #irus type 1 OR US8 gene polypeptide of MDV          - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: - # 33:                          - - Cys Leu Leu Tyr Tyr Val Tyr Glu Pro Cys Il - #e Tyr His Pro Arg Ala                        5 - #                  - #10                  - #15            - - Pro Glu Cys Leu Arg Pro Val Asp Pro Ala Cy - #s Ser Phe Thr Ser Pro                    20     - #             25     - #             30                   - - Ala Arg Ala Ala Leu Val Ala Arg Arg Ala Ty - #r Ala Ser Cys Ser Pro                35         - #         40         - #         45                       - - Leu Leu Gly Asp Arg Trp Leu Thr Ala Cys Pr - #o Phe Asp Ala Phe Gly            50             - #     55             - #     60                           - - Glu Glu Val His Thr Asn Ala Thr Ala Asp Gl - #u Ser Gly Leu Tyr Val        65                 - # 70                 - # 75                 - # 80        - - Leu Val Met                                                                - -  - - (2) INFORMATION FOR SEQ ID NO:34:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                  (A) LENGTH:  95 amin - #o acids                                                (B) TYPE:  amino aci - #d                                                      (C) STRANDEDNESS:  sing - #le                                                  (D) TOPOLOGY:  linear                                                 - -     (ii) MOLECULE TYPE:  peptide                                           - -      (v) FRAGMENT TYPE:  internal fragment                                 - -     (vi) ORIGINAL SOURCE:                                                           (A) ORGANISM:  equine - #herpesvirus type 1 (EHV1)                    - -     (ix) FEATURE:                                                                   (A) NAME/KEY:  peptide - #of EHV1 gE polypeptide                               (B) LOCATION:  249 T - #O 343                                                  (D) OTHER INFORMATION: - # peptide homologous to gE of herpes                       simplex v - #irus type 1 OR US8 gene polypeptide of MDV          - -     (xi) SEQUENCE DESCRIPTION: SEQ ID NO: - # 34:                          - - Cys Asp Leu Phe Arg Val Phe Glu Thr Cys Il - #e Phe His Pro Thr Ala                        5 - #                  - #10                  - #15            - - Met Ala Cys Leu His Pro Glu Gln His Thr Cy - #s Ser Phe Thr Ser Pro                    20     - #             25     - #             30                   - - Ile Arg Ala Thr Lys Ile Leu His Arg Val Ty - #r Gly Asn Cys Ser Asp                35         - #         40         - #         45                       - - His Gly Asn Ser Trp Pro Ser Arg Cys His Se - #r Thr Leu Leu Gly Asn            50             - #     55             - #     60                           - - Arg Leu Tyr Phe Ile Gln Pro Ala Gln Asn Ar - #g Val Asp Leu Leu Phe        65                 - # 70                 - # 75                 - # 80        - - Lys Asp Thr Pro Ala Ser Ala Thr Gly Leu Ty - #r Val Phe Val Leu                            85 - #                 90 - #                 95             __________________________________________________________________________ 

What is claimed is:
 1. A method for reducing pathogenicity or virulence of a Marek's disease herpesvirus whereby a gene which encodes a glycoprotein selected from glycoproteins I and E is altered which reduces the pathogenicity or virulence of the Marek's disease herpesvirus.
 2. A method for attenuating a Marek's disease herpesvirus, the steps comprising:a) introducing one or more mutations in at least one gene which encodes a glycoprotein selected from glycoproteins I and E wherein the mutation causes the corresponding mutated gene to fail to produce a functional polypeptide to produce the attenuated Marek's disease herpesvirus; and b) isolating the attenuated Marek's disease virus.
 3. The method of claim 2 wherein the mutation is contained within a DNA sequence of the Marek's disease herpesvirus comprising identity to SEQ ID NO:1.
 4. The method of claim 2 wherein the gene is mutagenized by inserting a foreign gene into the gene wherein the foreign gene produces a functional foreign polypeptide in the virus to produce the attenuated Marek's disease herpesvirus.
 5. The method of either claim 2 or 3 wherein the mutation is selected from deletions, insertions of foreign DNA, and mutations introduced by site-directed mutagenesis. 